Document Detail

Effect of AT1 angiotensin-receptor blockade on structure and function of small arteries in SHR.
MedLine Citation:
PMID:  9268224     Owner:  NLM     Status:  MEDLINE    
The structure and function of small arteries of different vascular beds in spontaneously hypertensive rats (SHRs) are altered relative to Wistar-Kyoto (WKY) control rats, and these differences may be blunted under treatment with angiotensin-converting enzyme inhibitors. To determine whether this effect of angiotensin-converting enzyme inhibitors was caused by the interruption of the renin-angiotensin system, our experiments were conducted with an AT1 angiotensin-receptor antagonist to evaluate its ability to induce regression of hypertrophy of resistance arteries in SHRs. The result of treatment of SHRs with losartan, an orally active selective angiotensin AT1 receptor antagonist was examined at a low (20 mg/kg/day) and a high (60 mg/kg/day) oral dose in SHRs once blood pressure had been elevated for some time. SHRs were treated for 12 weeks with losartan. Blood pressure was significantly reduced by losartan treatment from 210 +/- 2 mm Hg in untreated SHRs to 181 +/- 1 mm Hg (low dose) and 156 +/- 4 mm Hg (high dose) (p < 0.01). Cardiac and aortic hypertrophy were dose-dependently reduced in treated SHRs. Coronary, renal, mesenteric, and femoral small arteries (luminal diameter, 200-250 microm) studied on an isometric wire myograph and pressurized mesenteric small arteries examined under isobaric conditions exhibited significant hypertrophy and inward remodeling in SHRs in comparison to WKY rats. Losartan treatment resulted in a dose-dependent reduction in the media thickness and mediato-lumen ratio in small arteries from the four vascular beds studied on the wire myograph and in pressurized mesenteric small arteries. Endothelium-dependent relaxation studied in pressurized arteries was enhanced, and acetylcholine-induced endothelium-dependent contractions studied on the wire myograph were abolished in losartan-treated SHRs relative to untreated SHRs. In WKY rats, treatment had no effect. These results demonstrate that treatment with the selective angiotensin II receptor antagonist losartan, even at doses that reduce blood pressure only moderately, induces regression of cardiovascular hypertrophy and of endothelial dysfunction in genetic hypertension in the rat.
J S Li; A M Sharifi; E L Schiffrin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  30     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1997 Jul 
Date Detail:
Created Date:  1997-10-01     Completed Date:  1997-10-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  75-83     Citation Subset:  IM    
MRC Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.
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MeSH Terms
Aorta / drug effects
Arteries / drug effects*,  pathology,  physiopathology
Biphenyl Compounds / pharmacology*
Blood Pressure / drug effects
Coronary Vessels / drug effects,  pathology,  physiopathology
Dose-Response Relationship, Drug
Femoral Artery / drug effects,  pathology,  physiopathology
Heart / drug effects
Imidazoles / pharmacology*
Mesenteric Arteries / drug effects,  pathology,  physiopathology
Muscle Contraction / drug effects
Muscle, Smooth, Vascular / drug effects*,  pathology,  physiopathology
Organ Size / drug effects
Rats, Inbred SHR
Rats, Inbred WKY
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin / antagonists & inhibitors*
Renal Artery / drug effects,  pathology,  physiopathology
Renin / blood
Tetrazoles / pharmacology*
Reg. No./Substance:
0/Biphenyl Compounds; 0/Imidazoles; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 0/Tetrazoles; 114798-26-4/Losartan; EC

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