Obese female SHHF/Mcc-fa(cp) rats resist antihypertensive effects of renin-angiotensin system inhibition

Clinical and Experimental Hypertension : CHE
L C SharkeyM Judith Radin

Abstract

Gender and obesity may influence response to pharmacological modulation of the renin-angiotensin system. We used SHHF/Mcc-fa(cp) rats to study effect of obesity and gender on the ability of an AT1 receptor antagonist to decrease blood pressure. After 2 weeks treatment with irbesartan (50 mg/kg), only lean and obese males showed significant decreases in blood pressure, while obese females were completely resistant. Lean females showed a trend toward lowering of pressure (p=0.06). However, irbesartan similarly shifted angiotensin II dose response curves to the right in all groups. Twelve weeks of irbesartan also failed to decrease blood pressure, but did significantly reduce heart weight in obese females. In untreated rats, obese females had lower plasma renin activity and serum angiotensin converting enzyme activity compared to lean males, while lean and obese females had increased urinary endothelin excretion. Despite an otherwise similar genetic background contributing to hypertension and heart failure, obese females have different patterns of humoral activation compared to lean males, which may contribute to their resistance to the depressor effects of irbesartan.

References

Sep 1, 1989·Clinical Pharmacology and Therapeutics·T WalleE C Conradi
Jun 20, 1996·The New England Journal of Medicine·T L GoodfriendK J Catt
Oct 1, 1995·Acta Physiologica Scandinavica·H ScholzA Kurtz
Aug 1, 1996·Journal of Applied Physiology·D L GeenenP M Buttrick
Mar 15, 1997·The American Journal of Cardiology·K A Spratt
Jan 1, 1997·Endothelium : Journal of Endothelial Cell Research·D NigroM H Carvalho

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Citations

Jan 15, 2010·Clinical and Translational Science·Rosemeire M Kanashiro-TakeuchiJoshua M Hare
Feb 5, 2005·American Journal of Hypertension·Leslie C SharkeyJohn Fray
Jul 2, 2004·Experimental Biology and Medicine·Sonhee C ParkM Judith Radin
Dec 8, 2007·Clinical Science·Rita C TostesMaria Helena C Carvalho
Feb 14, 2002·Journal of Applied Physiology·M Judith RadinSylvia A McCune

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