Gerard D'Angelo - Academia.edu (original) (raw)
Papers by Gerard D'Angelo
Journal of Medicinal Chemistry, Mar 8, 2013
American Journal of Physiology-heart and Circulatory Physiology, Feb 1, 2002
Phosphorylation of the actinassociated protein caldesmon (CaD) by extracellular signalregulated k... more Phosphorylation of the actinassociated protein caldesmon (CaD) by extracellular signalregulated kinases (ERK1/2) is purported to participate in force maintenance by vascular smooth muscle. We examined the interrelationship among ERK1/2 activity, phosphorylation of the high molecular weight isoform of CaD (h-CaD) and the 20-kDa myosin light chain (LC20), and isometric force in strips of porcine carotid artery stimulated with endothelin-1 (ET-1; 50 nM). After an initial delay, ERK1/2 activity increased in parallel with ET-1-mediated force; h-CaD phosphorylation increased modestly. 2-(2Ј-Amino-3Ј-methoxyphenyl)-ox-anaphthalen-4-one (PD-098059; 50 M), an ERK1/2 kinase inhibitor, significantly reduced basal ERK1/2 activity within 1 h, but only partially attenuated h-CaD phosphorylation at 3 h. The mechanisms underlying the temporal dissociation of ERK1/2 activity from h-CaD phosphorylation are unknown, but include the possibility that a kinase other than ERK1/2 phosphorylates h-CaD or, more likely, that phosphate turnover in h-CaD is very slow. PD-098059 partially inhibited the development of ET-1-stimulated force only in Ca 2ϩ-replete physiological saline solution, primarily by reducing LC20 phosphorylation, yet had no effect on myosin light chain kinase in vitro. These inhibitory effects were most evident during the early phase of force production. The inhibitory effect of PD-098059 on force could not be correlated with a corresponding effect on ERK1/2-mediated h-CaD phosphorylation because force in arterial strips stimulated with ET-1 in the absence or presence of PD-098059 tended to approximate each other over time despite significant differences in the level of h-CaD phosphorylation. Force and LC20 phosphorylation in response to KCl depolarization were unaffected by PD-098059. These results show that ERK1/2 may regulate force in arterial smooth muscle, but suggest that the mechanism for this effect is by inhibiting LC 20 phosphorylation.
Hypertension, Jun 1, 1994
Vascular smooth muscle has the ability to exist in a state of maintained partial constriction. Th... more Vascular smooth muscle has the ability to exist in a state of maintained partial constriction. This state of partial activation is initiated and/or maintained by the mechanical effects of distending pressure acting on the vascular wall. The intrinsic ability of vascular smooth muscle to respond to these mechanical forces is referred to as the myogenic mechanism. Within the past decade the signaling mechanisms responsible for mechanotransduction of myogenic phenomena have been the focus of extensive research. Two areas of active investiga-From the
The FASEB Journal, Mar 1, 2006
American Journal of Physiology-Heart and Circulatory Physiology, 1997
The purpose of this study was to measure vascular smooth muscle (VSM) cytosolic calcium ([Ca2+]i)... more The purpose of this study was to measure vascular smooth muscle (VSM) cytosolic calcium ([Ca2+]i) during the myogenic response. We examined the temporal and steady-state relationships between lumen diameter and VSM [Ca2+]i in isolated arterioles exposed to step changes in intravascular pressure. We also studied the relationship between step sizes in intravascular pressure and changes in [Ca2+]i. First-order arterioles from the hamster cheek pouch were isolated, cannulated, and pressurized. [Ca2+]i was quantified using the ratio of emitted fluorescence intensity (R340/380) during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Stepwise increases in transmural pressure elicited corresponding increases in steady-state [Ca2+]i and myogenic constriction. From a common baseline pressure, the initial rise in [Ca2+]i after a step change in pressure was directly related to the magnitude of the step size and of the distension caused by that pressure step. This supports the th...
American Journal of Physiology-Heart and Circulatory Physiology, 1997
It has previously been shown that synthetic peptides containing the sequence arginine-glycine-asp... more It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0% reduction). In association with the decrease in [Ca2+]i, arteriolar lumen diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1...
Physiological reports, 2016
Insulin resistance is a powerful predictor of cardiovascular disease; however, the mechanistic li... more Insulin resistance is a powerful predictor of cardiovascular disease; however, the mechanistic link remains unclear. This study aims to determine if early cardiovascular changes associated with short-term fructose feeding in the absence of obesity manifest as abnormal blood pressure control. Metabolic dysfunction was induced in Lean Zucker rats by short-term high-fructose feeding. Rats were implanted with telemetry devices for the measurement of mean arterial blood pressure (MAP) and subjected to air jet stress at 5 and 8 weeks after feeding. Additional animals were catheterized under anesthesia for the determination of MAP and blood flow responses in the hind limb and mesenteric vascular beds to intravenous injection of isoproterenol (0.001-0.5 μm), a β-adrenergic agonist. Metabolic dysfunction in high-fructose rats was not accompanied by changes in 24-h MAP Yet, animals fed a high-fructose diet for 8 weeks exhibited a marked impairment in blood pressure recovery after air-jet stre...
Physiological reports, 2015
Acute stress in both rodents and humans causes a transient rise in blood pressure associated with... more Acute stress in both rodents and humans causes a transient rise in blood pressure associated with an increase in plasma endothelin-1 (ET-1). High salt (HS) intake also increases ET-1 production, and interestingly, blunts the pressor response to acute air jet stress in rats. We previously reported that female rats lacking functional ETB receptors everywhere except sympathetic nerves (ETB def) had a greater degree of hypertension in response to a HS diet compared to their male counterparts when measured by the tail cuff method. However, we now report that salt-induced hypertension is not different between sexes when measured by telemetry. Therefore, additional experiments were designed to test the hypothesis that female ETB def rats are more sensitive to acute stress when on a HS diet. The pressor response, measured by telemetry, to acute air jet stress was similar between male transgenic control (Tg control) and ETB def rats following chronic HS intake. In contrast, female ETB def ra...
American journal of physiology. Heart and circulatory physiology, 2002
Phosphorylation of the actin-associated protein caldesmon (CaD) by extracellular signal-regulated... more Phosphorylation of the actin-associated protein caldesmon (CaD) by extracellular signal-regulated kinases (ERK1/2) is purported to participate in force maintenance by vascular smooth muscle. We examined the interrelationship among ERK1/2 activity, phosphorylation of the high molecular weight isoform of CaD (h-CaD) and the 20-kDa myosin light chain (LC(20)), and isometric force in strips of porcine carotid artery stimulated with endothelin-1 (ET-1; 50 nM). After an initial delay, ERK1/2 activity increased in parallel with ET-1-mediated force; h-CaD phosphorylation increased modestly. 2-(2'-Amino-3'-methoxyphenyl)-ox-anaphthalen-4-one (PD-098059; 50 microM), an ERK1/2 kinase inhibitor, significantly reduced basal ERK1/2 activity within 1 h, but only partially attenuated h-CaD phosphorylation at 3 h. The mechanisms underlying the temporal dissociation of ERK1/2 activity from h-CaD phosphorylation are unknown, but include the possibility that a kinase other than ERK1/2 phosphory...
Journal of Medicinal Chemistry, 2013
Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in... more Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC 50 s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure−activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.
Journal of Biological Chemistry, 1999
Extracellular signal-regulated kinases (ERKs) phosphorylate the high molecular mass isoform of th... more Extracellular signal-regulated kinases (ERKs) phosphorylate the high molecular mass isoform of the actinbinding protein caldesmon (h-CaD) at two sites (Ser 759 and Ser 789) during smooth muscle stimulation. To investigate the role of phosphorylation at these sites, antibodies were generated against phosphopeptides analogous to the sequences around Ser 759 and Ser 789. Affinity-purified antibodies were phosho-and sequence-specific. The major site of phosphorylation in h-CaD in porcine carotid arterial muscle strips was at Ser 789 ; however, the amount of phosphate did not vary appreciably with either KCl or phorbol ester stimulation. Phosphorylation at Ser 759 of h-CaD was almost undetectable (<0.005 mol of phosphate/mol of protein). Moreover, phosphorylation of the low molecular mass isoform of the protein (l-CaD) at the site analogous to Ser 789 was greater in serum-stimulated cultured smooth muscle cells than in serum-starved cells. Serum-stimulated l-CaD phosphorylation was attenuated by the protein kinase inhibitor PD98059. These data 1) identify Ser 789 of h-CaD as the major site of ERK-dependent phosphorylation in carotid arteries; 2) show that the level of phosphorylation at Ser 789 is relatively constant following carotid arterial muscle stimulation, despite an increase in total protein phosphate content; and 3) suggest a functional role for ERK-dependent l-CaD phosphorylation in cell division. Caldesmon is an actin-, tropomyosin-, myosin-, and calmodulin-binding protein that is alternatively spliced to yield either a 93-kDa protein (high molecular mass caldesmon (h-CaD) 1), specific to contractile smooth muscle, or a 60-kDa protein (low molecular mass caldesmon (l-CaD)), expressed ubiquitously (1-3). h-CaD is an inhibitor of actomyosin ATPase activity and can tether actin filaments to myosin filaments, suggesting that it
Hypertension, 2010
Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen spec... more Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen species contribute to the pressor response induced by acute air jet stress in normotensive Dahl salt-sensitive rats maintained on a normal salt diet (prehypertensive). Mean arterial pressure was chronically monitored by telemetry before and after 3-day treatment with the free radical scavenger 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) or ET receptor antagonists ABT-627 (ET A antagonist) or A-182086 (ET A/B antagonist) supplied in the drinking water. Rats were restrained and subjected to pulsatile air jet stress (3 minutes). Plasma samples at baseline and during acute stress were analyzed for 8-isoprostane (measure of reactive oxygen species production) and ET. Neither Tempol nor ET receptor antagonist treatment had an effect on baseline mean arterial pressure or plasma 8-isoprostane. The pressor response to acute stress was accompanied by significant increases in plasma 8-isoprost...
Hypertension, 2005
Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly b... more Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected by long-term monitoring with telemetry in age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171±10 versus 120±10 mg/dL), plasma insulin (1.8±0.5 versus 0.7±0.1 μg/L), and plasma triglycerides (39±2 versus 30±2 mg/dL) were modestly but significantly elevated in fructose-fed animals. Using the hyperinsulinemic euglycemic clamp technique, the rate of glucose infusion necessary to maintain equivalent plasma glucose was significantly reduced in fructose-fed compared with control animals (22.9±3.6 versus 41.5±2.9 mg/kg per minute; P <0.05). However, mean arterial pressure (24-hour) did not change in the fructose-fed animals over the 8-week period (111±...
Journal of Medicinal Chemistry, Mar 8, 2013
American Journal of Physiology-heart and Circulatory Physiology, Feb 1, 2002
Phosphorylation of the actinassociated protein caldesmon (CaD) by extracellular signalregulated k... more Phosphorylation of the actinassociated protein caldesmon (CaD) by extracellular signalregulated kinases (ERK1/2) is purported to participate in force maintenance by vascular smooth muscle. We examined the interrelationship among ERK1/2 activity, phosphorylation of the high molecular weight isoform of CaD (h-CaD) and the 20-kDa myosin light chain (LC20), and isometric force in strips of porcine carotid artery stimulated with endothelin-1 (ET-1; 50 nM). After an initial delay, ERK1/2 activity increased in parallel with ET-1-mediated force; h-CaD phosphorylation increased modestly. 2-(2Ј-Amino-3Ј-methoxyphenyl)-ox-anaphthalen-4-one (PD-098059; 50 M), an ERK1/2 kinase inhibitor, significantly reduced basal ERK1/2 activity within 1 h, but only partially attenuated h-CaD phosphorylation at 3 h. The mechanisms underlying the temporal dissociation of ERK1/2 activity from h-CaD phosphorylation are unknown, but include the possibility that a kinase other than ERK1/2 phosphorylates h-CaD or, more likely, that phosphate turnover in h-CaD is very slow. PD-098059 partially inhibited the development of ET-1-stimulated force only in Ca 2ϩ-replete physiological saline solution, primarily by reducing LC20 phosphorylation, yet had no effect on myosin light chain kinase in vitro. These inhibitory effects were most evident during the early phase of force production. The inhibitory effect of PD-098059 on force could not be correlated with a corresponding effect on ERK1/2-mediated h-CaD phosphorylation because force in arterial strips stimulated with ET-1 in the absence or presence of PD-098059 tended to approximate each other over time despite significant differences in the level of h-CaD phosphorylation. Force and LC20 phosphorylation in response to KCl depolarization were unaffected by PD-098059. These results show that ERK1/2 may regulate force in arterial smooth muscle, but suggest that the mechanism for this effect is by inhibiting LC 20 phosphorylation.
Hypertension, Jun 1, 1994
Vascular smooth muscle has the ability to exist in a state of maintained partial constriction. Th... more Vascular smooth muscle has the ability to exist in a state of maintained partial constriction. This state of partial activation is initiated and/or maintained by the mechanical effects of distending pressure acting on the vascular wall. The intrinsic ability of vascular smooth muscle to respond to these mechanical forces is referred to as the myogenic mechanism. Within the past decade the signaling mechanisms responsible for mechanotransduction of myogenic phenomena have been the focus of extensive research. Two areas of active investiga-From the
The FASEB Journal, Mar 1, 2006
American Journal of Physiology-Heart and Circulatory Physiology, 1997
The purpose of this study was to measure vascular smooth muscle (VSM) cytosolic calcium ([Ca2+]i)... more The purpose of this study was to measure vascular smooth muscle (VSM) cytosolic calcium ([Ca2+]i) during the myogenic response. We examined the temporal and steady-state relationships between lumen diameter and VSM [Ca2+]i in isolated arterioles exposed to step changes in intravascular pressure. We also studied the relationship between step sizes in intravascular pressure and changes in [Ca2+]i. First-order arterioles from the hamster cheek pouch were isolated, cannulated, and pressurized. [Ca2+]i was quantified using the ratio of emitted fluorescence intensity (R340/380) during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Stepwise increases in transmural pressure elicited corresponding increases in steady-state [Ca2+]i and myogenic constriction. From a common baseline pressure, the initial rise in [Ca2+]i after a step change in pressure was directly related to the magnitude of the step size and of the distension caused by that pressure step. This supports the th...
American Journal of Physiology-Heart and Circulatory Physiology, 1997
It has previously been shown that synthetic peptides containing the sequence arginine-glycine-asp... more It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0% reduction). In association with the decrease in [Ca2+]i, arteriolar lumen diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1...
Physiological reports, 2016
Insulin resistance is a powerful predictor of cardiovascular disease; however, the mechanistic li... more Insulin resistance is a powerful predictor of cardiovascular disease; however, the mechanistic link remains unclear. This study aims to determine if early cardiovascular changes associated with short-term fructose feeding in the absence of obesity manifest as abnormal blood pressure control. Metabolic dysfunction was induced in Lean Zucker rats by short-term high-fructose feeding. Rats were implanted with telemetry devices for the measurement of mean arterial blood pressure (MAP) and subjected to air jet stress at 5 and 8 weeks after feeding. Additional animals were catheterized under anesthesia for the determination of MAP and blood flow responses in the hind limb and mesenteric vascular beds to intravenous injection of isoproterenol (0.001-0.5 μm), a β-adrenergic agonist. Metabolic dysfunction in high-fructose rats was not accompanied by changes in 24-h MAP Yet, animals fed a high-fructose diet for 8 weeks exhibited a marked impairment in blood pressure recovery after air-jet stre...
Physiological reports, 2015
Acute stress in both rodents and humans causes a transient rise in blood pressure associated with... more Acute stress in both rodents and humans causes a transient rise in blood pressure associated with an increase in plasma endothelin-1 (ET-1). High salt (HS) intake also increases ET-1 production, and interestingly, blunts the pressor response to acute air jet stress in rats. We previously reported that female rats lacking functional ETB receptors everywhere except sympathetic nerves (ETB def) had a greater degree of hypertension in response to a HS diet compared to their male counterparts when measured by the tail cuff method. However, we now report that salt-induced hypertension is not different between sexes when measured by telemetry. Therefore, additional experiments were designed to test the hypothesis that female ETB def rats are more sensitive to acute stress when on a HS diet. The pressor response, measured by telemetry, to acute air jet stress was similar between male transgenic control (Tg control) and ETB def rats following chronic HS intake. In contrast, female ETB def ra...
American journal of physiology. Heart and circulatory physiology, 2002
Phosphorylation of the actin-associated protein caldesmon (CaD) by extracellular signal-regulated... more Phosphorylation of the actin-associated protein caldesmon (CaD) by extracellular signal-regulated kinases (ERK1/2) is purported to participate in force maintenance by vascular smooth muscle. We examined the interrelationship among ERK1/2 activity, phosphorylation of the high molecular weight isoform of CaD (h-CaD) and the 20-kDa myosin light chain (LC(20)), and isometric force in strips of porcine carotid artery stimulated with endothelin-1 (ET-1; 50 nM). After an initial delay, ERK1/2 activity increased in parallel with ET-1-mediated force; h-CaD phosphorylation increased modestly. 2-(2'-Amino-3'-methoxyphenyl)-ox-anaphthalen-4-one (PD-098059; 50 microM), an ERK1/2 kinase inhibitor, significantly reduced basal ERK1/2 activity within 1 h, but only partially attenuated h-CaD phosphorylation at 3 h. The mechanisms underlying the temporal dissociation of ERK1/2 activity from h-CaD phosphorylation are unknown, but include the possibility that a kinase other than ERK1/2 phosphory...
Journal of Medicinal Chemistry, 2013
Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in... more Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC 50 s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure−activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.
Journal of Biological Chemistry, 1999
Extracellular signal-regulated kinases (ERKs) phosphorylate the high molecular mass isoform of th... more Extracellular signal-regulated kinases (ERKs) phosphorylate the high molecular mass isoform of the actinbinding protein caldesmon (h-CaD) at two sites (Ser 759 and Ser 789) during smooth muscle stimulation. To investigate the role of phosphorylation at these sites, antibodies were generated against phosphopeptides analogous to the sequences around Ser 759 and Ser 789. Affinity-purified antibodies were phosho-and sequence-specific. The major site of phosphorylation in h-CaD in porcine carotid arterial muscle strips was at Ser 789 ; however, the amount of phosphate did not vary appreciably with either KCl or phorbol ester stimulation. Phosphorylation at Ser 759 of h-CaD was almost undetectable (<0.005 mol of phosphate/mol of protein). Moreover, phosphorylation of the low molecular mass isoform of the protein (l-CaD) at the site analogous to Ser 789 was greater in serum-stimulated cultured smooth muscle cells than in serum-starved cells. Serum-stimulated l-CaD phosphorylation was attenuated by the protein kinase inhibitor PD98059. These data 1) identify Ser 789 of h-CaD as the major site of ERK-dependent phosphorylation in carotid arteries; 2) show that the level of phosphorylation at Ser 789 is relatively constant following carotid arterial muscle stimulation, despite an increase in total protein phosphate content; and 3) suggest a functional role for ERK-dependent l-CaD phosphorylation in cell division. Caldesmon is an actin-, tropomyosin-, myosin-, and calmodulin-binding protein that is alternatively spliced to yield either a 93-kDa protein (high molecular mass caldesmon (h-CaD) 1), specific to contractile smooth muscle, or a 60-kDa protein (low molecular mass caldesmon (l-CaD)), expressed ubiquitously (1-3). h-CaD is an inhibitor of actomyosin ATPase activity and can tether actin filaments to myosin filaments, suggesting that it
Hypertension, 2010
Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen spec... more Experiments were designed to test the hypothesis that endothelin (ET) and/or reactive oxygen species contribute to the pressor response induced by acute air jet stress in normotensive Dahl salt-sensitive rats maintained on a normal salt diet (prehypertensive). Mean arterial pressure was chronically monitored by telemetry before and after 3-day treatment with the free radical scavenger 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) or ET receptor antagonists ABT-627 (ET A antagonist) or A-182086 (ET A/B antagonist) supplied in the drinking water. Rats were restrained and subjected to pulsatile air jet stress (3 minutes). Plasma samples at baseline and during acute stress were analyzed for 8-isoprostane (measure of reactive oxygen species production) and ET. Neither Tempol nor ET receptor antagonist treatment had an effect on baseline mean arterial pressure or plasma 8-isoprostane. The pressor response to acute stress was accompanied by significant increases in plasma 8-isoprost...
Hypertension, 2005
Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly b... more Fructose feeding has been widely reported to cause hypertension in rats, as assessed indirectly by tail cuff plethysmography. Because there are potentially significant drawbacks associated with plethysmography, we determined whether blood pressure changes could be detected by long-term monitoring with telemetry in age-matched male Sprague-Dawley rats fed either a normal or high-fructose diet for 8 weeks. Fasting plasma glucose (171±10 versus 120±10 mg/dL), plasma insulin (1.8±0.5 versus 0.7±0.1 μg/L), and plasma triglycerides (39±2 versus 30±2 mg/dL) were modestly but significantly elevated in fructose-fed animals. Using the hyperinsulinemic euglycemic clamp technique, the rate of glucose infusion necessary to maintain equivalent plasma glucose was significantly reduced in fructose-fed compared with control animals (22.9±3.6 versus 41.5±2.9 mg/kg per minute; P <0.05). However, mean arterial pressure (24-hour) did not change in the fructose-fed animals over the 8-week period (111±...