Abstract
Acute intravenous prazosin (0.05 mg/kg) caused marked falls in mean arterial pressure and postsynaptic alpha 1-adrenoceptor blockade in rabbits. During chronic oral dosing (3--21 days), tolerance developed and blood pressure returned to base-line pretreatment levels. This did not appear to be related to changes in plasma renin activity, body weight, prazosin kinetics, or alpha 2-adrenoceptor responsiveness. However, pressor responses to the alpha 1-adrenoceptor agonist phenylephrine and the mixed alpha 1/alpha 2-agonist noradrenaline increased during chronic prazosin therapy. Despite the development of apparent "tolerance," the response to bolus injections of prazosin was unchanged. No changes in the maximum number of prazosin binding sites or their dissociation constant were observed in the heart, spleen, forebrain, or hindbrain after 21 days treatment. It appears that although compensatory mechanisms develop during chronic prazosin treatment, they are not mediated by alterations in alpha 1-receptor binding but are related to changes in alpha 1-adrenoceptor responsiveness beyond the drug-receptor binding site.
Citations
Jan 1, 1984·Naunyn-Schmiedeberg's Archives of Pharmacology·C A HamiltonD J Sumner
Sep 1, 1984·Basic Research in Cardiology·A BeckG Raberger
Oct 3, 1983·Life Sciences·J E WikbergP O Hagen
Oct 28, 1985·Life Sciences·M MazeB B Hoffman
Mar 1, 1986·Journal of the American College of Cardiology·M PackerM Yushak
Nov 1, 1992·The Journal of Clinical Investigation·J VincentB B Hoffman
Jan 1, 1989·Clinical and Experimental Hypertension. Part A, Theory and Practice·S M BarrJ L Reid
Nov 1, 1983·American Heart Journal·J W ConstantineR Weeks
Dec 1, 1993·Cancer·N I Cherny, R K Portenoy
Jan 1, 1982·Acta Medica Scandinavica. Supplementum·K E Andersson
Dec 1, 1989·Journal of Autonomic Pharmacology·M D Brown
Jan 1, 1988·Fundamental & Clinical Pharmacology·P Kerth, M Frisk-Holmberg
Apr 1, 1983·Naunyn-Schmiedeberg's Archives of Pharmacology·J A HannahJ L Reid