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The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and α1-adrenoceptors (α1- ARs) expression was explored., Alzet® minipumps filled with Ang II (200 ng kg−1 min−1) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1R antagonist, or with BMY 7378, a selective α1D- AR antagonist. Blood pressure was measured by tail-cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses., Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II-treated rats than in the controls, and similar effect occurred with KCl 80 m m. Responses in tail arteries were not significantly different among the different groups., Angiotensin II decreased α1D- ARs without modifying the other α1- ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II- AT1Rs and α1D- ARs. Angiotensin II-induced α1D- AR-mediated vascular remodeling occurs independently of hypertension., Findings identify a α1D- AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation. [ABSTRACT FROM AUTHOR]

We investigated captopril effects, an ACE inhibitor, on hypertension development, on Ang II and Ang-(1-7) plasma concentrations, on Ang II-induced contraction in isolated kidneys, and on kidney AT1R from spontaneously hypertensive (SHR) rats., Five weeks-old SHR and Wistar Kyoto (WKY) rats were treated with captopril at 30 mg/kg/day, in drinking water for 2 or 14 weeks. Systolic blood pressure (SBP) was measured, and isolated kidneys were tested for perfusion pressure and AT1R expression; while Ang II and Ang-(1-7) concentrations were determined in plasma., Captopril did not modify SBP in WKY rats and avoided its increase as SHR aged. Plasma Ang-II concentration was ∼4-5 folds higher in SHR rats, and captopril reduced it (P < 0.05); while captopril increased Ang-(1-7) by ∼2 fold in all rat groups., Captopril increased Ang II-induced pressor response in kidneys of WKY and SHR rats, phenomenon not observed in kidneys stimulated with phenylephrine, a α1-adrenoceptor agonist., Captopril did not modify AT1R in kidney cortex and medulla among rat strains and ages., Data indicate that captopril increased Ang II-induced kidney perfusion pressure but not AT1R density in kidney of WKY and SHR rats, due to blockade of angiotensin II synthesis; however, ACE inhibitors may have other actions like activating signaling processes that could contribute to their diverse effects. [ABSTRACT FROM AUTHOR]

1 The hypothesis that α1D-adrenoceptors may mediate the pro-hypertensive actions of angiotensin II (Ang II) was tested in isolated aorta (α1D-adrenoceptor bearing tissue) of the aryl hydrocarbon receptor null mouse (AhR−/−), which shows increased levels of Ang II, cardiac hypertrophy and hypertension. 2 The effect of captopril (an angiotensin converting enzyme inhibitor) on both blood pressure and aortic α1D-adrenoceptor expression and function in mice were determined. 3 Basal blood pressure was higher in AhR−/− mice, while captopril therapy decreased it to wild-type (WT) values. 4 Aortas of adult WT and AhR−/− mice were stimulated by phenylephrine or noradrenaline to induce contraction; the maximal effect was higher in AhR−/− mice, without a significant change in pEC50. 5 PA2 values for the selective α1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazynil]ethyl]-8-azaspiro [4.5]decane-7,9-dione) were 9.19 and 8.94 for WT and AhR−/−, respectively; while Schild slopes were not different from 1. 6 PCR experiments showed c. 77% increase in AhR−/−α1D-adrenoceptors cDNA compared with WT mice; while western blot analysis demonstrated c. 88% increase in α1D-adrenoceptor protein in AhR−/− mice. 7 Captopril therapy decreased α1D-adrenoceptor-induced contraction and protein in AhR−/− mice to WT levels. 8 These data support the hypothesis that under conditions where Ang II is elevated, vascular α1D-adrenoceptors are increased, and further suggest that both Ang II and vascular α1D-adrenoceptors could be related in the onset of hypertension. [ABSTRACT FROM AUTHOR]

1 Multiple α1-adrenoceptors were evaluated in caudal artery of the young Wistar rat using selective agonists and antagonists. 2 Arteries were exposed to the selective α1A-adrenoceptor agonist, A-61603 ( N-[5-(4,5-dihydro-1 H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl] methanesulfonamide) or to phenylephrine and to prazosin ( α1-adrenoceptor antagonist), or the selective α1A-adrenoceptor antagonists 5-methylurapidil, RS 100329 (5-methyl-3-[3-[4-[2-(2,2,2,-trifluoroethoxy)phenyl]-1-piperazinyl]propyl]-2,4-(1 H)-pyrimidinedione), RS 17053 ( N-[2(2-cyclopropylmethoxy) ethyl]-5-chloro- α, α-dimethyl-1 H-indole-3-ethanamide), and the selective α1D-adrenoceptor antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5] decane-7,9-dione). 3 Results showed a 100-fold higher potency of A-61603 for the α1-adrenoceptor present in the artery, compared with phenylephrine. Prazosin displaced both agonists with high affinity, whereas 5-methylurapidil, RS 100329 and RS 17053 displaced A-61603 with high affinity, indicating the presence of α1A-adrenoceptors. 4 The selective α1A-adrenoceptor antagonists blocked phenylephrine responses with low affinity, suggesting that phenylephrine activated a second receptor population in caudal artery. 5 BMY 7378 antagonized with low affinity both A-61603 and phenylephrine-induced contractions, indicating absence of α1D-adrenoceptors in the vessel. 6 The results suggest that functional α1B-adrenoceptors are present in caudal arteries of the young Wistar rat. [ABSTRACT FROM AUTHOR]

1 The effect of WAY 405 ((R)- N-(2-methyl-(4-indolyl-1-piperazinyl)ethyl)- N-(2-pyridinyl) cyclohexane carboxamide), a putative 5-HT1A receptor antagonist, on cardiovascular function was studied. 2 In anaesthetized rats, the i.v. injection of WAY 405 did not significantly modify basal heart rate nor blood pressure at doses of 1, 3, 10 and 30 μg kg−1; while the antagonist dose dependently antagonized the 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di- n-propylamino)tetralin)-induced hypotension and bradycardia. 3 WAY 405 antagonized noradrenaline-induced contraction in isolated arteries, with p KB values of 6.6 ± 0.1, 6.5 ± 0.1 and 6.5 ± 0.1, for rat tail artery ( α1A-adrenoceptors), rabbit aorta ( α1B-adrenoceptors), and rat aorta ( α1D-adrenoceptors) respectively. 4 The results show that in the control of blood pressure the new compound, WAY 405, behaves as a silent 5-HT1A receptor antagonist in the anaesthetized rat, also having low affinity for vascular α1-adrenoceptors. [ABSTRACT FROM AUTHOR]

1 The pressor action of noradrenaline and its blockade by selective α1-adrenoceptor antagonists in the pithed mouse were evaluated. 2 Chloroethylclonidine ( α1B/D-adrenoceptor alkylating agent) or BMY 7378 ( α1D-adrenoceptor antagonist), both at 1 mg kg−1, did not block the increase in blood pressure induced by noradrenaline. 3 5-Methylurapidil ( α1A-adrenoceptor antagonist), at 0.1 mg kg−1, displaced the dose–response curve approximately six-fold to the right. 4 The results support the idea that the pithed mouse vasculature express α1A-adrenoceptors and suggest that it is a good model to study the roles of α1-adrenoceptors in gene knockout or overexpression. [ABSTRACT FROM AUTHOR]