R. Tackett - Academia.edu (original) (raw)
Papers by R. Tackett
BACKGROUND Telehealth-based dietary interventions were recommended for cardiovascular disease (CV... more BACKGROUND Telehealth-based dietary interventions were recommended for cardiovascular disease (CVD) management during the COVID-19 pandemic; however, data regarding their effectiveness and feasibility are limited. OBJECTIVE To examine (1) the effectiveness of telehealth-based dietary interventions in improving clinical CVD risk factors and (2) their feasibility among CVD patients. METHODS To conduct this systematic review and meta-analysis of randomized controlled trials (RCTs), two investigators searched PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov databases based on predetermined search terms, and included English language RCTs published between January 2000 and July 2022. Pooled data for each CVD outcome were assessed using a random effects model. Mean difference (MD), standardized MD (SMD), or risk ratio (RR) were calculated using R software. RESULTS A total of 13 RCTs with 3,013 participants were included in the analysis. Participants had a mean age (SD) of ...
Research in Social and Administrative Pharmacy
Pharmacology, 1989
The present study examined the interaction of opioidergic systems in the hypotensive action of at... more The present study examined the interaction of opioidergic systems in the hypotensive action of atenolol. Anesthetized, adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were instrumented to monitor blood pressure and heart rate. Atenolol (100 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude in both SHR and WKY rats. However, the bradycardia was greater in SHR. Pretreatment with naloxone (0.1 mg/kg, i.v.) 15 min prior to the administration of atenolol completely prevented the hypotensive response in SHR and decreased the maximum hypotensive response by approximately 50% in WKY rats. The atenolol-induced bradycardia was unaffected in both groups of animals. Additionally, pretreatment with yohimbine, an alpha 2-receptor antagonist, inhibited the hypotensive response of atenolol in SHR. Collectively, these results suggest an interaction between opioidergic and catecholaminergic systems as a possible site of action of antihypertensive drugs.
Annals of Pharmacotherapy, 2011
The FASEB Journal
The objective of this study was to test the hypothesis that there are interactions between copper... more The objective of this study was to test the hypothesis that there are interactions between copper (Cu) and selenium (Se) status, and adriamycin (ADR) toxicity. Male Sprague Dawley rats were fed Cu,Se adequate; Cu deficient, Se adequate (-Cu); Cu adequate, Se deficient; or Cu,Se deficient diets for 38-41 days. ADR or saline (SAL) were administered weekly for the last 4 weeks of the study. Cu deficiency was confirmed by a 3-fold decrease in liver Cu,Zn-superoxide dismutase and liver Cu, and a 5-fold decrease in RBC Cu,Zn-SOD. Se deficiency was confirmed by a 10-fold decrease in liver glutathione peroxidase (GSH-Px). ADR, Cu deficiency and Se deficiency all caused EKG abnormalities. However, Cu and Se deficiencies did not enhance ADR's influence on EKGs. ADR increased lipid peroxidation in liver by 15% and in heart by 18% (NS). Cu deficiency decreased ADR-induced lipid peroxidation in heart tissue by 25%. ADR influenced Se status by significantly increasing heart GSH-Px, and Cu sta...
The Journal of Thoracic and Cardiovascular Surgery, 1996
Journal of Pharmaceutical Sciences, 1992
Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) ... more Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 26-day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (?/oCV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brainserum AZT concentration ratios were 0.1 26 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state >1 pM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy.
Analytical Letters - ANAL LETT, 1987
A simple and sensitive method has been developed for the determination of disopyramide employing ... more A simple and sensitive method has been developed for the determination of disopyramide employing reverse phase high performance liquid chromatography with UV detection. p-Chlorodisopyramide was used as an internal standard. The retention times of disopyramide and the internal standard at an elution rate of 1.8 ml/min were 6.28 and 8.78 min, respectively.
Journal of chromatography. B, Biomedical sciences and applications, 2000
Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synth... more Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synthase (NOS) and is important in the regulation of vascular tone, neurotransmission and host defense. N,N-Dimethyl L-arginine (asymmetric dimethylarginine, ADMA) and N-monomethyl L-arginine (MMA) are endogenous inhibitors of NOS. N,N'-Dimethyl L-arginine (symmetric dimethylarginine, SDMA), the inactive enantiomer of ADMA is also known to be present endogenously. A simple, sensitive and fast LC-MS-MS method was developed to extract and quantitate ADMA, SDMA, MMA and ARG from human plasma. 13C6-ARG was used as the internal standard for the assay. Protein precipitation using acetonitrile gave good recoveries of all the compounds from plasma. The compounds were separated by HPLC in less than 15 min using a silica column. The limits of detection for this method were found to be approximately 1 ng/ml for ARG, ADMA and SDMA and 2.5 ng/ml for MMA. The total LC-MS-MS analysis time is less than 1...
American journal of veterinary research, 1999
To compare in vitro smooth muscle relaxation of palmar digital vessels from healthy horses with t... more To compare in vitro smooth muscle relaxation of palmar digital vessels from healthy horses with those from horses in the prodromal stage of experimentally (carbohydrate) induced laminitis. 16 adult horses. Segments of palmar digital vessels were obtained from 5 healthy horses and 6 horses given carbohydrate. Vascular rings from the palmar digital artery and vein were suspended in individual organ baths containing buffer solution and indomethacin; isometric tension was recorded, and contraction and relaxation were compared. Smooth muscle contraction in response to cumulative addition of phenylephrine was recorded in the absence and presence of 1 microM NG-nitro-L-arginine methyl ester (L -NAME). After wash out, vascular rings were preconstricted with phenylephrine (0.3 microM), and cumulative endothelium-dependent (acetylcholine-induced) and independent (nitroprusside-induced) smooth muscle relaxations were recorded in the absence or presence of L -NAME. Phenylephrine increased vascu...
The Journal of pharmacology and experimental therapeutics, 1998
The present study determined the vasomotor effects of oxidized low-density lipoprotein (ox-LDL) i... more The present study determined the vasomotor effects of oxidized low-density lipoprotein (ox-LDL) in human saphenous veins and determined whether decreased availability of L-arginine was responsible for the impaired endothelial function. Human saphenous veins were obtained from white males undergoing coronary bypass surgery. We examined the effects of ox-LDL on ACh-induced endothelium-dependent relaxation, sodium nitroprusside-induced endothelium-independent relaxation and 5-HT-induced contraction. ACh-induced vasorelaxation in the presence of L-arginine and ox-LDL was also examined. In addition, we assessed the endothelial influence on the contractile response to 5-HT. ox-LDL significantly inhibited ACh-induced relaxation but did not affect sodium nitroprusside-induced relaxation. L-Arginine pretreatment did not prevent ox-LDL-induced impairment of the relaxation response to ACh. ox-LDL significantly potentiated 5-HT-induced contraction at concentrations between 3 x 10(-6) M and 10(-...
Veterinary Surgery, 1989
Peripheral vasoconstriction and plasma catecholamine concentrations were studied in 37 dogs after... more Peripheral vasoconstriction and plasma catecholamine concentrations were studied in 37 dogs after cervical disc fenestration and salivary gland excision, laparotomy for intestinal anastomoses and cystotomy, or laparotomy for repair of diaphragmatic rupture, gastrotomy, and pyloromyotomy. Meperidine (4.4 mg/kg) was administered before extubation of 12 dogs undergoing laparotomy. Heart rate, respiratory frequency, indirect blood pressure, rectal temperature, toe web temperature, and plasma concentrations of epinephrine and norepinephrine were determined before induction of anesthesia, after intubation, after extubation, at sternal recumbency, and at standing. All dogs were hypothermic during surgery. After surgery, peripheral hypothermia (large rectal-toe web temperature gradients) increased from a mean of 4.6OC after intubation to a mean of 10.4OC when the dogs initially stood. Heart and respiratory rates and blood pressures during recovery were similar to those before anesthesia. Mean plasma catecholamine concentrations were neither significantly higher during recovery than before surgery nor were they increased in any surgical group, including the dogs not treated with meperidine. After anesthesia, 15% of the epinephrine and 12% of the norepinephrine samples were more than two standard deviations above the mean of the preanesthetic concentrations of all dogs. The ratio of all dogs with an epinephrine,concentration more than two standard deviations above the mean of baseline epinephrine concentrations was greater at sternal recumbency than before anesthesia and the ratio of dogs with an increased epinephrine concentration at sternal recumbency was greater in the laparotomy dogs (9 of 24) than in the cervical surgery dogs (0 of 12). Decreased peripheral blood flow during recovery from anesthesia appears to be a homeostatic attempt of conserving body heat to correct the hypothermia produced by anesthesia and peripheral vasodilation.
Pharmacology, 1985
Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response ... more Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response of certain vasoactive compounds. Responses of rabbit thoracic aorta to verapamil, diltiazem, nitroglycerin and isoproterenol were examined in zero Mg2+ (0.0 M), N Mg2+ (1.2 mM), 2 N Mg2+ (2.4 mM) and 4 N Mg2+ (4.8 mM). Preconstriction was induced with norepinephrine and cumulative dose-response curves were obtained for the vasodilators. The dose-response curve for isoproterenol was shifted to the right in zero Mg2+ while there was no effect on the other vasodilators. Elevation of the Mg2+ concentration to 4.8 mM produced a shift to the left in the dose-response curves for diltiazem, nitroglycerin and isoproterenol with no effect on verapamil. Therefore, Mg2+ deficiency does not appear to affect the vasodilatory actions of the agents tested except for the beta-receptor agonist, isoproterenol. Elevated Mg2+, however, potentiated the actions of isoproterenol, nitroglycerin and diltiazem, but not verapamil.
Life Sciences, 1987
Central administration of BHT 933, a highly selective alpha 2 agonist, to pentobarbital-anestheti... more Central administration of BHT 933, a highly selective alpha 2 agonist, to pentobarbital-anesthetized, normotensive dogs resulted in a rapid, significant decrease in blood pressure. The maximal response occurred at 30 min and remained significantly decreased for 60 min. Concomitant with the hypotensive response was a decrease in heart rate. Pretreatment with naloxone 15 min prior to the administration of BHT 933 completely abolished the hypotensive response and significantly inhibited the bradycardia. These results suggest a role for central opioidergic systems in the control of blood pressure which may serve as important sites of antihypertensive drug action. The central regulation of sympathetic tone by catecholaminergic systems plays an important role in the control of cardiovascular function in both normal and pathological states. A high density of catecholaminergic nerve terminals is found in regions of the brainstem involved in cardiovascular control. Stimulation of the alpha receptors in these areas decreases peripheral sympathetic tone and subsequently lowers blood pressure. Recent histochemical evidence has demonstrated the presence of opioid peptides in the nucleus tractus solitarii, nucleus ambiguous and hypothalamus as well as other discrete brain areas associated with cardiovascular control. Activation of the opiate receptors in these brain areas decreases sympathetic tone and blood pressure. Additionally, both catecholaminergic and opioidergic systems have been implicated in the reaction to certain stimuli (i.e., pain, stress) which entail important hemodynamic adaptations. The similarity between the central opiate and catecholaminergic systems suggests a relationship between the two systems in blood pressure control and a potential site of antihypertensive drug action. The purpose of the present study was to determine if an opioidergic component is involved in the hypotensive action of BHT 933 (azepexole). BHT 933 is a relatively new hypotensive agent which is a much more specific alpha 2 agonist than clonidine.
Journal of Pharmacy and Pharmacology, 1987
The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific... more The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific dopaminergic agonists and antagonists were administered into the ventriculocisternal system of pentobarbitone-anaesthetized dogs before systemic administration of digoxin. Pretreatment with apomorphine, a specific dopamine agonist, did not significantly alter the arrhythmogenic or lethal doses of digoxin. However, the digoxin-induce increase in CSF noradrenaline was decreased significantly in apomorphine-pretreated animals. Pretreatment with pimozide, a specific dopamine antagonist, significantly decreased the arrhythmogenic dose of digoxin but did not alter the lethal dose. As with apomorphine, pimozide-pretreated animals accumulated significantly less noradrenaline in CSF compared with control dogs. These results suggest that dopamine receptors are not directly related to the cardiotoxic actions of digoxin. However, dopaminergic receptors may influence the balance of central catecholaminergic systems that influence the peripheral cardiovascular system.
Journal of Chromatography, 1998
Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase... more Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase high-performance liquid chromatography of eleven eicosanoids. Separation and quantitation by ultraviolet absorbance at 190 nm using conventional-bore ODS columns were compared. Using the improved sensitivity obtained by means of the narrow-bore column, i.e. 250-pg detection limits of a standard solution, analysis of eicosanoids in kidney medulla was achieved. Parallel quantitation by radioactivity, using [1-(14)C]arachidonic acid as substrate, was applied.
Equine Veterinary Journal, 2000
The in vitro responses of isolated vascular preparations of digital arteries and veins obtained f... more The in vitro responses of isolated vascular preparations of digital arteries and veins obtained from healthy anaesthetised horses were determined for dopamine and fenoldopam. The digital vessels were harvested, cut into 4 mm vascular segments, suspended in tissue baths and attached to force-displacement transducers. Dose-response studies between 10(-8) and 10(-4)M concentrations were performed for all drugs. The change in tension of each vascular ring was measured in grams of force. The reactivity between palmar and plantar digital vessels and baseline vascular responses were determined for dopamine. The vascular responses of dopamine were compared to in vitro data for other known vasoconstrictor agents. The mechanism of vasoconstriction induced by dopamine was further defined using prazosin, a specific competitive alpha-1 adrenoceptor antagonist. The vasodilating ability of fenoldopam, a dopamine-1 (DA-1) receptor agonist, was also determined using noradrenaline- preconstricted vascular segments from palmar digital vessels. The effective concentration to produce 50 per cent of the maximal response (EC50) and the maximal contraction in grams of force per milligram of the vascular ring (g/mg) were calculated. There were no differences in the reactivity between the palmar and plantar digital vessels. Dopamine produced intense constriction in arteries and veins but only at very high molar concentrations. Prazosin decreased significantly the sensitivity of the veins to dopamine (increased the mean EC50 values) but not the arteries. Prazosin had no effect on the maximal contractions of the vessels. Fenoldopam produced very little relaxation of either the arteries or veins. These results suggest that dopamine produces constriction in equine digital arteries and veins and that the constriction is only partially mediated by alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research Bulletin, 1990
Biopharmaceutics & Drug Disposition, 1987
The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in health... more The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in healthy mongrel dogs following intravenous and oral administration of the drug. The free fraction of tiazofurin was obtained from plasma by an ultrafiltration technique using a micropartition system. Total and free tiazofurin levels were determined by a sensitive high performance liquid chromatographic method. The percentage of tiazofurin bound to plasma proteins remained constant at approximately 15 per cent following administration to healthy mongrel dogs. The mean pharmacokinetic parameters of elimination rate constant (K), effective half-life (t 1/2), mean residence time (MRT) and the time to reach peak plasma level (tmax--after oral administration) were 0.32 +/- 0.04 h-1, 2.24 +/- 0.25 h, 3.23 +/- 0.36 h, and 1.78 +/- 0.50 h, respectively. The apparent volume of distribution at steady state was 0.98 +/- 0.30 1 kg-1 and the plasma clearance was 5.24 +/- 2.39 ml min-1 kg-1. About 90 per cent of tiazofurin was absorbed following oral administration. The pharmacokinetic parameters did not differ significantly between the total and free drug levels, indicating that the pharmacokinetics of total tiazofurin levels reflect those of the free tiazofurin in plasma.
BACKGROUND Telehealth-based dietary interventions were recommended for cardiovascular disease (CV... more BACKGROUND Telehealth-based dietary interventions were recommended for cardiovascular disease (CVD) management during the COVID-19 pandemic; however, data regarding their effectiveness and feasibility are limited. OBJECTIVE To examine (1) the effectiveness of telehealth-based dietary interventions in improving clinical CVD risk factors and (2) their feasibility among CVD patients. METHODS To conduct this systematic review and meta-analysis of randomized controlled trials (RCTs), two investigators searched PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov databases based on predetermined search terms, and included English language RCTs published between January 2000 and July 2022. Pooled data for each CVD outcome were assessed using a random effects model. Mean difference (MD), standardized MD (SMD), or risk ratio (RR) were calculated using R software. RESULTS A total of 13 RCTs with 3,013 participants were included in the analysis. Participants had a mean age (SD) of ...
Research in Social and Administrative Pharmacy
Pharmacology, 1989
The present study examined the interaction of opioidergic systems in the hypotensive action of at... more The present study examined the interaction of opioidergic systems in the hypotensive action of atenolol. Anesthetized, adult spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were instrumented to monitor blood pressure and heart rate. Atenolol (100 micrograms/kg, i.v.) produced a decrease in blood pressure of similar magnitude in both SHR and WKY rats. However, the bradycardia was greater in SHR. Pretreatment with naloxone (0.1 mg/kg, i.v.) 15 min prior to the administration of atenolol completely prevented the hypotensive response in SHR and decreased the maximum hypotensive response by approximately 50% in WKY rats. The atenolol-induced bradycardia was unaffected in both groups of animals. Additionally, pretreatment with yohimbine, an alpha 2-receptor antagonist, inhibited the hypotensive response of atenolol in SHR. Collectively, these results suggest an interaction between opioidergic and catecholaminergic systems as a possible site of action of antihypertensive drugs.
Annals of Pharmacotherapy, 2011
The FASEB Journal
The objective of this study was to test the hypothesis that there are interactions between copper... more The objective of this study was to test the hypothesis that there are interactions between copper (Cu) and selenium (Se) status, and adriamycin (ADR) toxicity. Male Sprague Dawley rats were fed Cu,Se adequate; Cu deficient, Se adequate (-Cu); Cu adequate, Se deficient; or Cu,Se deficient diets for 38-41 days. ADR or saline (SAL) were administered weekly for the last 4 weeks of the study. Cu deficiency was confirmed by a 3-fold decrease in liver Cu,Zn-superoxide dismutase and liver Cu, and a 5-fold decrease in RBC Cu,Zn-SOD. Se deficiency was confirmed by a 10-fold decrease in liver glutathione peroxidase (GSH-Px). ADR, Cu deficiency and Se deficiency all caused EKG abnormalities. However, Cu and Se deficiencies did not enhance ADR's influence on EKGs. ADR increased lipid peroxidation in liver by 15% and in heart by 18% (NS). Cu deficiency decreased ADR-induced lipid peroxidation in heart tissue by 25%. ADR influenced Se status by significantly increasing heart GSH-Px, and Cu sta...
The Journal of Thoracic and Cardiovascular Surgery, 1996
Journal of Pharmaceutical Sciences, 1992
Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) ... more Zidovudine (AZT), prepared as an alkaline solution, was administered iv and intraarterially (ia) by continuous infusion via an implantable pump in dogs. The AZT serum and cerebrospinal fluid (CSF) concentrations were measured over a 26-day treatment period by HPLC. Terminal brain AZT concentrations were also measured. Control (vehicle only) animals were also studied. All animals were evaluated for pathological changes associated with the AZT and vehicle infusions in catheterized vessels and other organs. In the iv AZT treatment group, serum AZT concentrations were relatively constant, with individual coefficients of variations (?/oCV) of 20% or less. Mean CSF:serum and brain:serum AZT concentration ratios were 0.149 and 0.212, respectively. In the ia AZT treatment group, serum AZT concentrations were more variable than in the iv group, with %CV ranging from 22 to 79%. The fluctuations in serum concentrations were attributed to temporary blockages of the outflow catheter. Mean CSF:serum and brainserum AZT concentration ratios were 0.1 26 and 0.249, respectively. Pathological changes, similar in both control and treatment groups, included endothelial denudation and myointimal proliferation at the infusion sites. The conclusions of the study are (1) steady-state >1 pM AZT serum concentrations can be maintained chronically by use of an implantable pump containing a basic pH AZT solution; (2) ia delivery of AZT did not increase central nervous system uptake compared with iv administration; and (3) morbidity associated with the infused solutions does not seem to be a limitation for this mode of therapy.
Analytical Letters - ANAL LETT, 1987
A simple and sensitive method has been developed for the determination of disopyramide employing ... more A simple and sensitive method has been developed for the determination of disopyramide employing reverse phase high performance liquid chromatography with UV detection. p-Chlorodisopyramide was used as an internal standard. The retention times of disopyramide and the internal standard at an elution rate of 1.8 ml/min were 6.28 and 8.78 min, respectively.
Journal of chromatography. B, Biomedical sciences and applications, 2000
Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synth... more Nitric oxide (NO) is synthesized from L-arginine (ARG) catalyzed by the enzyme nitric oxide synthase (NOS) and is important in the regulation of vascular tone, neurotransmission and host defense. N,N-Dimethyl L-arginine (asymmetric dimethylarginine, ADMA) and N-monomethyl L-arginine (MMA) are endogenous inhibitors of NOS. N,N'-Dimethyl L-arginine (symmetric dimethylarginine, SDMA), the inactive enantiomer of ADMA is also known to be present endogenously. A simple, sensitive and fast LC-MS-MS method was developed to extract and quantitate ADMA, SDMA, MMA and ARG from human plasma. 13C6-ARG was used as the internal standard for the assay. Protein precipitation using acetonitrile gave good recoveries of all the compounds from plasma. The compounds were separated by HPLC in less than 15 min using a silica column. The limits of detection for this method were found to be approximately 1 ng/ml for ARG, ADMA and SDMA and 2.5 ng/ml for MMA. The total LC-MS-MS analysis time is less than 1...
American journal of veterinary research, 1999
To compare in vitro smooth muscle relaxation of palmar digital vessels from healthy horses with t... more To compare in vitro smooth muscle relaxation of palmar digital vessels from healthy horses with those from horses in the prodromal stage of experimentally (carbohydrate) induced laminitis. 16 adult horses. Segments of palmar digital vessels were obtained from 5 healthy horses and 6 horses given carbohydrate. Vascular rings from the palmar digital artery and vein were suspended in individual organ baths containing buffer solution and indomethacin; isometric tension was recorded, and contraction and relaxation were compared. Smooth muscle contraction in response to cumulative addition of phenylephrine was recorded in the absence and presence of 1 microM NG-nitro-L-arginine methyl ester (L -NAME). After wash out, vascular rings were preconstricted with phenylephrine (0.3 microM), and cumulative endothelium-dependent (acetylcholine-induced) and independent (nitroprusside-induced) smooth muscle relaxations were recorded in the absence or presence of L -NAME. Phenylephrine increased vascu...
The Journal of pharmacology and experimental therapeutics, 1998
The present study determined the vasomotor effects of oxidized low-density lipoprotein (ox-LDL) i... more The present study determined the vasomotor effects of oxidized low-density lipoprotein (ox-LDL) in human saphenous veins and determined whether decreased availability of L-arginine was responsible for the impaired endothelial function. Human saphenous veins were obtained from white males undergoing coronary bypass surgery. We examined the effects of ox-LDL on ACh-induced endothelium-dependent relaxation, sodium nitroprusside-induced endothelium-independent relaxation and 5-HT-induced contraction. ACh-induced vasorelaxation in the presence of L-arginine and ox-LDL was also examined. In addition, we assessed the endothelial influence on the contractile response to 5-HT. ox-LDL significantly inhibited ACh-induced relaxation but did not affect sodium nitroprusside-induced relaxation. L-Arginine pretreatment did not prevent ox-LDL-induced impairment of the relaxation response to ACh. ox-LDL significantly potentiated 5-HT-induced contraction at concentrations between 3 x 10(-6) M and 10(-...
Veterinary Surgery, 1989
Peripheral vasoconstriction and plasma catecholamine concentrations were studied in 37 dogs after... more Peripheral vasoconstriction and plasma catecholamine concentrations were studied in 37 dogs after cervical disc fenestration and salivary gland excision, laparotomy for intestinal anastomoses and cystotomy, or laparotomy for repair of diaphragmatic rupture, gastrotomy, and pyloromyotomy. Meperidine (4.4 mg/kg) was administered before extubation of 12 dogs undergoing laparotomy. Heart rate, respiratory frequency, indirect blood pressure, rectal temperature, toe web temperature, and plasma concentrations of epinephrine and norepinephrine were determined before induction of anesthesia, after intubation, after extubation, at sternal recumbency, and at standing. All dogs were hypothermic during surgery. After surgery, peripheral hypothermia (large rectal-toe web temperature gradients) increased from a mean of 4.6OC after intubation to a mean of 10.4OC when the dogs initially stood. Heart and respiratory rates and blood pressures during recovery were similar to those before anesthesia. Mean plasma catecholamine concentrations were neither significantly higher during recovery than before surgery nor were they increased in any surgical group, including the dogs not treated with meperidine. After anesthesia, 15% of the epinephrine and 12% of the norepinephrine samples were more than two standard deviations above the mean of the preanesthetic concentrations of all dogs. The ratio of all dogs with an epinephrine,concentration more than two standard deviations above the mean of baseline epinephrine concentrations was greater at sternal recumbency than before anesthesia and the ratio of dogs with an increased epinephrine concentration at sternal recumbency was greater in the laparotomy dogs (9 of 24) than in the cervical surgery dogs (0 of 12). Decreased peripheral blood flow during recovery from anesthesia appears to be a homeostatic attempt of conserving body heat to correct the hypothermia produced by anesthesia and peripheral vasodilation.
Pharmacology, 1985
Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response ... more Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response of certain vasoactive compounds. Responses of rabbit thoracic aorta to verapamil, diltiazem, nitroglycerin and isoproterenol were examined in zero Mg2+ (0.0 M), N Mg2+ (1.2 mM), 2 N Mg2+ (2.4 mM) and 4 N Mg2+ (4.8 mM). Preconstriction was induced with norepinephrine and cumulative dose-response curves were obtained for the vasodilators. The dose-response curve for isoproterenol was shifted to the right in zero Mg2+ while there was no effect on the other vasodilators. Elevation of the Mg2+ concentration to 4.8 mM produced a shift to the left in the dose-response curves for diltiazem, nitroglycerin and isoproterenol with no effect on verapamil. Therefore, Mg2+ deficiency does not appear to affect the vasodilatory actions of the agents tested except for the beta-receptor agonist, isoproterenol. Elevated Mg2+, however, potentiated the actions of isoproterenol, nitroglycerin and diltiazem, but not verapamil.
Life Sciences, 1987
Central administration of BHT 933, a highly selective alpha 2 agonist, to pentobarbital-anestheti... more Central administration of BHT 933, a highly selective alpha 2 agonist, to pentobarbital-anesthetized, normotensive dogs resulted in a rapid, significant decrease in blood pressure. The maximal response occurred at 30 min and remained significantly decreased for 60 min. Concomitant with the hypotensive response was a decrease in heart rate. Pretreatment with naloxone 15 min prior to the administration of BHT 933 completely abolished the hypotensive response and significantly inhibited the bradycardia. These results suggest a role for central opioidergic systems in the control of blood pressure which may serve as important sites of antihypertensive drug action. The central regulation of sympathetic tone by catecholaminergic systems plays an important role in the control of cardiovascular function in both normal and pathological states. A high density of catecholaminergic nerve terminals is found in regions of the brainstem involved in cardiovascular control. Stimulation of the alpha receptors in these areas decreases peripheral sympathetic tone and subsequently lowers blood pressure. Recent histochemical evidence has demonstrated the presence of opioid peptides in the nucleus tractus solitarii, nucleus ambiguous and hypothalamus as well as other discrete brain areas associated with cardiovascular control. Activation of the opiate receptors in these brain areas decreases sympathetic tone and blood pressure. Additionally, both catecholaminergic and opioidergic systems have been implicated in the reaction to certain stimuli (i.e., pain, stress) which entail important hemodynamic adaptations. The similarity between the central opiate and catecholaminergic systems suggests a relationship between the two systems in blood pressure control and a potential site of antihypertensive drug action. The purpose of the present study was to determine if an opioidergic component is involved in the hypotensive action of BHT 933 (azepexole). BHT 933 is a relatively new hypotensive agent which is a much more specific alpha 2 agonist than clonidine.
Journal of Pharmacy and Pharmacology, 1987
The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific... more The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific dopaminergic agonists and antagonists were administered into the ventriculocisternal system of pentobarbitone-anaesthetized dogs before systemic administration of digoxin. Pretreatment with apomorphine, a specific dopamine agonist, did not significantly alter the arrhythmogenic or lethal doses of digoxin. However, the digoxin-induce increase in CSF noradrenaline was decreased significantly in apomorphine-pretreated animals. Pretreatment with pimozide, a specific dopamine antagonist, significantly decreased the arrhythmogenic dose of digoxin but did not alter the lethal dose. As with apomorphine, pimozide-pretreated animals accumulated significantly less noradrenaline in CSF compared with control dogs. These results suggest that dopamine receptors are not directly related to the cardiotoxic actions of digoxin. However, dopaminergic receptors may influence the balance of central catecholaminergic systems that influence the peripheral cardiovascular system.
Journal of Chromatography, 1998
Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase... more Mobile-phase variations were employed to achieve optimal separation by narrow-bore reversed-phase high-performance liquid chromatography of eleven eicosanoids. Separation and quantitation by ultraviolet absorbance at 190 nm using conventional-bore ODS columns were compared. Using the improved sensitivity obtained by means of the narrow-bore column, i.e. 250-pg detection limits of a standard solution, analysis of eicosanoids in kidney medulla was achieved. Parallel quantitation by radioactivity, using [1-(14)C]arachidonic acid as substrate, was applied.
Equine Veterinary Journal, 2000
The in vitro responses of isolated vascular preparations of digital arteries and veins obtained f... more The in vitro responses of isolated vascular preparations of digital arteries and veins obtained from healthy anaesthetised horses were determined for dopamine and fenoldopam. The digital vessels were harvested, cut into 4 mm vascular segments, suspended in tissue baths and attached to force-displacement transducers. Dose-response studies between 10(-8) and 10(-4)M concentrations were performed for all drugs. The change in tension of each vascular ring was measured in grams of force. The reactivity between palmar and plantar digital vessels and baseline vascular responses were determined for dopamine. The vascular responses of dopamine were compared to in vitro data for other known vasoconstrictor agents. The mechanism of vasoconstriction induced by dopamine was further defined using prazosin, a specific competitive alpha-1 adrenoceptor antagonist. The vasodilating ability of fenoldopam, a dopamine-1 (DA-1) receptor agonist, was also determined using noradrenaline- preconstricted vascular segments from palmar digital vessels. The effective concentration to produce 50 per cent of the maximal response (EC50) and the maximal contraction in grams of force per milligram of the vascular ring (g/mg) were calculated. There were no differences in the reactivity between the palmar and plantar digital vessels. Dopamine produced intense constriction in arteries and veins but only at very high molar concentrations. Prazosin decreased significantly the sensitivity of the veins to dopamine (increased the mean EC50 values) but not the arteries. Prazosin had no effect on the maximal contractions of the vessels. Fenoldopam produced very little relaxation of either the arteries or veins. These results suggest that dopamine produces constriction in equine digital arteries and veins and that the constriction is only partially mediated by alpha-1 adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Research Bulletin, 1990
Biopharmaceutics & Drug Disposition, 1987
The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in health... more The pharmacokinetics of total and free tiazofurin, an antineoplastic agent, was studied in healthy mongrel dogs following intravenous and oral administration of the drug. The free fraction of tiazofurin was obtained from plasma by an ultrafiltration technique using a micropartition system. Total and free tiazofurin levels were determined by a sensitive high performance liquid chromatographic method. The percentage of tiazofurin bound to plasma proteins remained constant at approximately 15 per cent following administration to healthy mongrel dogs. The mean pharmacokinetic parameters of elimination rate constant (K), effective half-life (t 1/2), mean residence time (MRT) and the time to reach peak plasma level (tmax--after oral administration) were 0.32 +/- 0.04 h-1, 2.24 +/- 0.25 h, 3.23 +/- 0.36 h, and 1.78 +/- 0.50 h, respectively. The apparent volume of distribution at steady state was 0.98 +/- 0.30 1 kg-1 and the plasma clearance was 5.24 +/- 2.39 ml min-1 kg-1. About 90 per cent of tiazofurin was absorbed following oral administration. The pharmacokinetic parameters did not differ significantly between the total and free drug levels, indicating that the pharmacokinetics of total tiazofurin levels reflect those of the free tiazofurin in plasma.