Hypotensive effects of eugenosedin-A with serotonin, alpha- and beta-adrenoceptor antagonistic activities in spontaneously hypertensive and normotensive rats (original) (raw)
Related papers
European Journal of Pharmacology, 1987
The present experiments served to compare the effects of the 3 5-HT 1 agonists, 8-OH-DPAT, 5-MeODMT and TFMPP on the blood pressure and heart rate of normotensive anaesthetized rats. All the agonists induced, after i.v. injection, a decrease in blood pressure and heart rate. The hypotensive effects of 5-MeODMT and TFMPP were preceded by an increase, suppressed by both ketanserin and methysergide. The decrease in blood pressure induced by 5-MeODMT and 8-OH-DPAT was not antagonized by ketanserin, cocaine (and methysergide for 8-OH-DPAT) but was antagonized by methysergide (for 5-MeODMT) and spiroxatrine (for both). Bradycardia was not susceptible to ketanserin and cocaine (for 5-MeODMT) or to ketanserin and methysergide (for 8-OH-DPAT) but to methysergide and spiroxatrine (for 5-MeODMT) and cocaine and spiroxatrine (for 8-OH-DPAT). These results suggested that the hypotension and bradycardia induced by 5-MeODMT and 8-OH-DPAT are due to the stimulation of '5-HTl-like' receptors and probably to the 5-HTIA subtype; the 5-MeODMT-induced hypertension being ascribed to the stimulaiton of 5-HT 2 receptors. 8-OH-DPAT (8-hydroxy-2(di-N-propylamino)tetralin);
European Journal of Pharmacology, 2006
This study set out to analyse the potential ability of some 5-hydroxytryptamine (5-HT) receptor ligands widely used in cardiovascular experimental models to interact with vascular α 1 -adrenoceptors in the pithed rat. These ligands included: methiothepin, methysergide and metergoline (5-HT 1 /5-HT 2 ); WAY-100635, buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT 1A ); GR127935 (5-HT 1B/1D ); ketanserin, ritanserin, spiperone and pizotifen (5-HT 2 ); granisetron and metoclopramide (5-HT 3 ); tropisetron (5-HT 3 / 5-HT 4 ); ergotamine (5-HT 1B/1D , 5-ht 5A/5B ); clozapine (5-HT 6 /5-HT 7 ); as well as LY215840 and mesulergine (5-HT 2 /5-HT 7 ). For this purpose, the increases in diastolic blood pressure produced by the selective α 1 -adrenoceptor agonist, phenylephrine, were analysed before and after the above antagonists or saline. The adrenoceptor antagonist properties of prazosin (α 1 ) and yohimbine (α 2 ) were also analysed for comparison. Thus, the phenylephrine-induced vasopressor responses were dose-dependently antagonised with the following apparent rank order of potency by: prazosin ≥ methiothepin N ketanserin N clozapine ≥ lisuride ≫ buspirone; this potency correlates with the affinity of these compounds for α 1adrenoceptor binding sites. In contrast, the other compounds were either devoid of any blocking effect onor even potentiated (i.e. lisuride, methysergide, 8-OH-DPAT, granisetron and GR127935)the responses to phenylephrine. These results show that methiothepin, ketanserin, clozapine, lisuride and buspirone can block α 1 -adrenoceptors in the rat systemic vasculature.
European journal of pharmacology, 2006
This study set out to analyse the potential ability of some 5-hydroxytryptamine (5-HT) receptor ligands widely used in cardiovascular experimental models to interact with vascular alpha1-adrenoceptors in the pithed rat. These ligands included: methiothepin, methysergide and metergoline (5-HT(1)/5-HT2); WAY-100635, buspirone, ipsapirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (5-HT(1A)); GR127935 (5-HT(1B/1D)); ketanserin, ritanserin, spiperone and pizotifen (5-HT2); granisetron and metoclopramide (5-HT3); tropisetron (5-HT3/5-HT4); ergotamine (5-HT(1B/1D), 5-ht(5A/5B)); clozapine (5-HT6/5-HT7); as well as LY215840 and mesulergine (5-HT2/5-HT7). For this purpose, the increases in diastolic blood pressure produced by the selective alpha1-adrenoceptor agonist, phenylephrine, were analysed before and after the above antagonists or saline. The adrenoceptor antagonist properties of prazosin (alpha1) and yohimbine (alpha2) were also analysed for comparison. Thus, the phenyle...
British Journal of Pharmacology, 1998
1 Desensitization of the myocardial b-adrenergic signal transduction pathway is an important mechanism which is involved in the progression of hypertensive heart disease. The aim of the present study was to evaluate the dierential eects of chronic pharmacotherapy with an angiotensin converting enzyme (ACE)-inhibitor, an AT 1 -receptor antagonist and a direct vasodilator on blood pressure, cardiac hypertrophy and the b-adrenergic signal transduction. Therefore, transgenic TG(mREN2)27 (TG) rats overexpressing the mouse renin gene were used. This strain is characterized by the development of fulminant hypertension with cardiac hypertrophy. 2 Seven week old heterozygous TG(mREN2)27 rats were treated for 11 weeks with the AT 1 -receptor antagonist losartan (10 mg kg 71 ), the ACE-inhibitor quinapril (15 mg kg 71 ) and the direct vasodilator hydralazine (30 mg kg 71 ). Untreated TG and normotensive Sprague-Dawley rats (SD) served as controls.
(S)-UH-301 antagonizes (R)-8-OH-DPAT-indiiced cardiovascular effects in the rat
European Journal of Pharmacology, 1991
The 5-HT,,-receptor antagonist WUH-301 (S)-5-fluoro-8-hydroxy-2-(dipropylamino)tetralin) completely antagonized the hypotension and bradycardia induced by (RI = S-OH DPAT t(R)-8-hydroxy-2-(dipropylamino)tetralin) in conscious rats. W-UH-301 alone induced a weak hypertension, which might be due to its 5-HT,,-receptor antagonistic properties. (RI-UH301 induced effects similar to those of (RI-8-OH DPAT, i.e., a short initial phase of hypertension followed by a long-lasting hypotension and bradycardia. Thus, (RI-UH301 behaves as a 5-HT,,-receptor agonist and (S)-UH301 as a 5-HT,,-receptor antagonist, abolishing the effects induced by (RI-8-OH DPAT.
Journal of Biomedical Science, 1996
The purpose of this study was to determine whether 13-adrenergically mediated Propranolol cardiovascular functions such as arterial pressure (AP), heart rate (HR), stroke Atenolol volume (SV), cardiac output (CO), peripheral resistance (Rp), arterial impe-Hemodynamics dance (Zc), mean arterial compliance (Cm) and pulse wave reflection (Pb) were Arterial impedance altered in the spontaneously hypertensive rat (SHR) compared to the normo-Hypertension tensive Wistar Kyoto rat (WKY). In pentobarbital-anesthetized and artificially ventilated rats, the aortic pressure wave was recorded with a high-fidelity Millar sensor, and aortic flow wave with an electromagnetic flow probe. The pressure and flow waves were subjected to Fourier transform so as to analyze impedance spectra. Acute [3-adrenergic blockade was produced by an intravenous injection ofpropranolol (nonselective) and atenolol (selective 131-blocker) at doses of 2 and 5 mg/kg, respectively. Steady-state parameters were obtained 15-20 min after intravenous administration. The SHR had higher AP, HR, Rp and Zc than the WKY. SV and CO remained unaltered while Cm was lower. In response to propranolol, the mean AP was increased by 7 mm Hg in the WKY, but did not change in the SHR. Moreover, significant decreases occurred in HR, CO and Cm in addition to increases in Rp, Zc and Pb. These changes between the SHR and WKY were only slight. Atenolol caused decreases in AP, HR and CO in both SHR and WKY, but did not significantly alter the Rp, Zc, Cm and Pb. Again, the atenolol-induced changes in AP, HR and CO did not appear to be significantly different between SHR and WKY. The results indicate that [~-adrenergic effects on the heart, Windkessel and resistance vessels are neither greatly enhanced nor impaired during the development of hypertension. In the hypertensive state, significant [3-adrenergic mechanisms still exert tonic vasodilatory effects on the large and small arterial system.
Hypertension, 1991
The purpose of this study was to examine in vivo the importance of angiotensin subtype 1 (AT,) versus subtype 2 (AT 2) receptors in spontaneously hypertensive (hypertensive) versus normotensive Wistar-Kyoto (control) rats. Intravenous infusions of DuP 753, a selective AT, receptor antagonist, abolished the pressor responses to intravenous infusions of angiotensin II in both strains, and the potency of DuP 753 in this regard was similar in the two strains. DuP 753 also abolished angiotensin II-induced aldosterone release in both strains; however, with respect to inhibiting angiotensin II-induced aldosterone release, DuP 753 was more potent in hypertensive compared with control rats. In hypertensive but not control rats, DuP 753 inhibited angiotensin II-induced aldosterone release at doses lower than required to inhibit angiotensin II-induced pressor responses. Intramesenteric infusions of DuP 753 abolished mesenteric vascular responses to intramesenteric infusions of angiotensin II with a similar potency in both strains. In control but not hypertensive rats, angiotensin II consistently potentiated noradrenergic neurotransmission in the mesenteric vascular bed, and this effect of angiotensin II was abolished by DuP 753. High doses of PD123177, a selective AT 2 antagonist, did not influence any of the aforementioned effects of angiotensin II in either strain. These data indicate that I) in both hypertensive and control rats, AT, receptors mediate the acute effects of angiotensin II on arterial blood pressure, aldosterone release, and mesenteric vascular resistance; 2) in control rats, AT, receptors mediate the effects of angiotensin II on noradrenergic neurotransmission; and 3) spontaneously hypertensive rats are more sensitive to DuP 753-induced blockade of angiotensin II-mediated aldosterone release compared with Wistar-Kyoto control rats, at least under the conditions of this study. (Hypertension 1991;18:774-782) I n 1982, Furukawa et al 1 described in a US patent a series of imidazole-5-acetic acid compounds that relaxed blood vessels preconstricted with angiotensin II (Ang II) and lowered blood pressure in rats receiving infusions of Ang II. In 1988, Wong et al 2 and Chiu et al 3 characterized two of these compounds, S-8307 and S-8308, as highly selective and competitive, albeit weak, nonpeptide Ang II receptor antagonists. In 1989 and 1990, a flurry of reports, originating from investigators at the E.I. du Pont de Nemours and Company, described improvements on the lead compounds that resulted in much more potent, and in some cases orally active, selective
Zagazig University Medical Journal, 2017
Background: In treatment of hypertension, care should be taken for preventing hypertensive organ injuries as well as lowering blood pressure to the adequate level in order to decrease the risk of cardiovascular and renal diseases. Objectives: To assess and compare the possible protective effect of various angiotensin receptor blockers namely candesartan, olmesartan, telmisartan ,and valsaratn on cardiovascular and renal tissues in renal hypertensive rats Methods: In this study 72 adult male albino rats were used and divided into six equal groups (each of 12 rats): Group 1, control normal received the vehicle; Group 2, control renal hypertensive induced by left renal artery ligation received the vehicle and Group 3 treated renal hypertensive rats which is divided into four subgroups: subgroup (A) received candesartan (0.1 mg/kg/day); subgroup (B) received olmesartan (3mg/kg/day); subgroup (C) received telmisartan (0.5 mg/kg/day),and subgroup (D) received valsartan (0.5 mg/kg/day). Rats received drugs orally by gavage once daily for 2 weeks. Results: The present study revealed that left renal artery ligation induced significant increases in mean arterial blood pressure (MABP), heart rate (HR), heart weight, cardiac fibrosis and glomerulosclerosis. Also, there were significant increases in serum level of tumor necrosis factor alpha (TNF-α), cardiac level of inteleukin1β (IL1β), and cardiac and renal levels of malondialdehyde (MDA) concomitant with significant reduction in cardiac and renal level of reduced glutathione (GSH). MABP was similarly reduced in candesartan, olmesartan, telmisartan and valsartan groups compared to control renal hypertensive group. Heart rate, cardiac weight, and cardiac fibrosis were significantly reduced in telmisartan and candesartan group. Telmisartan and candesartan suppressed serum level of TNFα and the cardiac level of IL-1β. Meanwhile, olmesartan and valsartan significantly decreased glomerulosclerosis index and renal level of MDA with significant increase in renal level of GSH. Conclusion: Telmisartan and candesartan exerted better cardioprotective effect via prevention of inflammatory cascade, and olmesartan and valsartan exerted better renoprotective effect via enhancement of antioxidant capacity.