Document Detail


Effects of renin-angiotensin blockade on sympathetic reactivity and beta-adrenergic pathway in the spontaneously hypertensive rat.
MedLine Citation:
PMID:  9260993     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
As interactions between the renin-angiotensin and sympathetic nervous systems have been suggested in the pathogenesis of hypertension, we wanted to investigate the effect of chronic renin-angiotensin blockade with losartan and enalaprilat on the sympathetic reactivity to hypotension and on the cardiac beta-adrenergic-coupled adenylyl cyclase pathway in 12-week-old Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Both treatments, exerting equipotent shifts of angiotensin-pressure responses, lowered blood pressure and attenuated cardiac hypertrophy similarly in SHR. The nitroprusside-induced hypotension was similar in both strains, but the associated increases in plasma catecholamines and heart rate were higher in SHR. In SHR treated with losartan and enalaprilat, the nitroprusside-induced hypotension was greater and associated with markedly attenuated increases in norepinephrine and heart rate. The binding affinity of cardiac beta-adrenoceptors was significantly lower, and beta2-adrenoceptor subtype was dominant in untreated SHR in contrast to WKY, in which beta1-adrenoceptor subtype was dominant. Enalaprilat treatment increased total beta-adrenoceptor density, whereas both treatments restored the binding affinity and beta1- and beta2-adrenoceptor proportions to normal in SHR. Isoproterenol-, guanylylimidodiphosphate [Gpp(NH)p]-, and forskolin-stimulated adenylyl cyclase reactivity was increased in SHR. Enalaprilat restored adenylyl cyclase reactivity to normal in SHR and reduced the sensitivity (EC50) of Gpp(NH)p-induced cAMP formation in both strains. The present study supports the possibility that functional alterations of the renin-angiotensin and sympathetic systems are involved in hypertension in SHR. The antihypertensive action of losartan and enalaprilat in SHR may be partly mediated through the normalization of sympathetic hyperreactivity and the restoration of beta-adrenergic signaling pathway sensitivity.
Authors:
A K-Laflamme; L Oster; R Cardinal; J de Champlain
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hypertension     Volume:  30     ISSN:  0194-911X     ISO Abbreviation:  Hypertension     Publication Date:  1997 Aug 
Date Detail:
Created Date:  1997-09-11     Completed Date:  1997-09-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  278-87     Citation Subset:  IM    
Affiliation:
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Québec, Canada. laflaman@ere.umontreal.ca
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MeSH Terms
Descriptor/Qualifier:
Adenylate Cyclase / metabolism
Angiotensin-Converting Enzyme Inhibitors / pharmacology*
Angiotensins / pharmacology
Animals
Antihypertensive Agents / pharmacology*
Biphenyl Compounds / pharmacology*
Blood Pressure / drug effects
Enalaprilat / pharmacology*
Hypertension / complications,  metabolism,  physiopathology*
Hypertrophy, Left Ventricular / etiology,  pathology
Imidazoles / pharmacology*
Losartan
Male
Myocardium
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Receptors, Adrenergic, beta / drug effects*,  metabolism,  physiology
Reflex / physiology
Renin-Angiotensin System / drug effects*
Sympathetic Nervous System / drug effects*,  physiopathology
Tetrazoles / pharmacology*
Chemical
Reg. No./Substance:
0/Angiotensin-Converting Enzyme Inhibitors; 0/Angiotensins; 0/Antihypertensive Agents; 0/Biphenyl Compounds; 0/Imidazoles; 0/Receptors, Adrenergic, beta; 0/Tetrazoles; 114798-26-4/Losartan; 84680-54-6/Enalaprilat; EC 4.6.1.1/Adenylate Cyclase

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


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