Pharmacodynamic Contribution to the Vasodilator Effect of Chronic AT(1) Receptor Blockade in SHR

Jeremy R A PaullR E Widdop


-The present study investigated the pharmacodynamic contribution of AT(1) receptor blockade to the regional hemodynamic effects of long-term treatment with the AT(1) receptor antagonist candesartan cilexetil in adult spontaneously hypertensive rats (SHR). Blood pressure and Doppler flowmetry measurements were made during and after withdrawal of candesartan cilexetil, representing times of maximal and negligible blockade of AT(1) receptor-mediated vasoconstriction. There was marked renal, mesenteric, and hindquarter vasodilation in SHR treated for 4 weeks with candesartan cilexetil (2 mg/kg per day in drinking water, n=8) compared with vehicle (n=8). Blood pressure increased after withdrawal of candesartan cilexetil but was still reduced after 6 days, whereas regional flows and conductances did not reduce significantly compared with the last day of treatment. There was more prolonged inhibition of angiotensin (Ang) I-induced than Ang II-induced pressor responses after withdrawal of candesartan cilexetil, but these returned to control levels before blood pressure reached fully hypertensive levels. The renal and mesenteric vasoconstrictor effects of exogenously administered Ang I and Ang II returned to control levels just 2 days a...Continue Reading


Apr 1, 1991·American Journal of Hypertension·J E PintoJ M Saavedra
Aug 1, 1995·Journal of Cardiovascular Pharmacology·D J CampbellA J Valentijn
Jul 1, 1997·Journal of Cardiovascular Pharmacology·J S LiE L Schiffrin

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Mar 11, 2004·Current Hypertension Reports·Ruth E Hannan, Robert E Widdop
Jan 15, 2002·American Journal of Physiology. Renal Physiology·Bernardo Rodríguez-IturbeHéctor A Pons

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