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Type: Journal article
Title: Functional tolerance to a-adrenergic receptor blockade in the spontaneously hypertensive rat highlights the multi-functional role of vascular angiotensin II in the development of hypertension
Author: Smid, S.
Frewin, D.
Wyartt, C.
Head, R.
Citation: Journal of Vascular Research, 1995; 32(4):247-253
Publisher: S. Karger
Issue Date: 1995
ISSN: 1018-1172
Statement of
S.D. Smid, D.B. Frewin, C.L. Wyartt and R.J. Head
Abstract: Treatment of spontaneously hypertensive rats (SHR) with α-adrenoceptor antagonists failed to alter the development of hypertension in this animal model. However, agents such as captopril (CAP) and losartan (LOS) which interfere with the renin-angiotensin system effectively prevented the development of hypertension. When tolerance occurred in the presence of doxazosin (DOX) or phenoxybenzamine, there was an enhanced sensitivity to the blood pressure lowering influence of LOS. In the presence of CAP, at a dose that did not retard the development of blood pressure in the SHR, DOX treatment significantly offset the development of hypertension in this strain. These results suggest that a functional tolerance to agents that interfere with the sympathetic nervous system is mediated by the renin-angiotensin system. Angiotensin-converting enzyme inhibition was associated with a normalization of the enhanced contraction of the mesenteric vascular bed seen in preparations from the SHR and a suppression in the development of the vascular amplifier. The results suggest that the sympathetic nervous system is unable to maintain an elevated blood pressure in the SHR during interference with the functioning of the renin-angiotensin system. Conversely, under conditions of α-adrenoceptor blockade, angiotensin II can maintain an elevated blood pressure in the SHR
Keywords: Animals
Rats, Inbred SHR
Rats, Inbred WKY
Biphenyl Compounds
Angiotensin II
Adrenergic alpha-Antagonists
Blood Pressure
Drug Tolerance
DOI: 10.1159/000159099
Description (link):
Appears in Collections:Aurora harvest 2
Pharmacology publications

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