Document Detail

Functional tolerance to alpha-adrenergic receptor blockade in the spontaneously hypertensive rat highlights the multifunctional role of vascular angiotensin II in the development of hypertension.
MedLine Citation:
PMID:  7654881     Owner:  NLM     Status:  MEDLINE    
Treatment of spontaneously hypertensive rats (SHR) with alpha-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 alpha-adrenoceptor blockade, angiotensin II can maintain an elevated blood pressure in the SHR.
S D Smid; D B Frewin; C L Wyartt; R J Head
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of vascular research     Volume:  32     ISSN:  1018-1172     ISO Abbreviation:  J. Vasc. Res.     Publication Date:    1995 Jul-Aug
Date Detail:
Created Date:  1995-10-05     Completed Date:  1995-10-05     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  SWITZERLAND    
Other Details:
Languages:  eng     Pagination:  247-53     Citation Subset:  IM    
Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia.
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MeSH Terms
Adrenergic alpha-Antagonists / therapeutic use*
Angiotensin II / physiology*
Biphenyl Compounds / administration & dosage,  therapeutic use
Blood Pressure
Captopril / administration & dosage,  therapeutic use
Doxazosin / administration & dosage,  therapeutic use
Drug Tolerance
Hypertension / drug therapy*,  physiopathology
Imidazoles / administration & dosage,  therapeutic use
Norepinephrine / pharmacology
Phenoxybenzamine / administration & dosage,  therapeutic use
Rats, Inbred SHR
Rats, Inbred WKY
Tetrazoles / administration & dosage,  therapeutic use
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Biphenyl Compounds; 0/Imidazoles; 0/Tetrazoles; 11128-99-7/Angiotensin II; 114798-26-4/Losartan; 51-41-2/Norepinephrine; 59-96-1/Phenoxybenzamine; 62571-86-2/Captopril; 74191-85-8/Doxazosin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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