Pressor response to beta 1- and beta 2-blockers in conscious rats treated with phentolamine.
The purpose of this study was to examine the conditions whereby beta-blockers cause a pressor response in conscious, unrestrained rats: (1) whether beta-blockers cause a pressor response in rats subjected to, or not subjected to, nonselective alpha-blockade with phentolamine; (2) whether the pressor response to beta-blockers is due to the blockade of vasodilator beta 2-adrenoceptors, and (3) whether it is due to an acute increase in the release of adrenaline (A) and noradrenaline (NA). In the first series of experiments cumulative dose-response curves for propranolol, atenolol and ICI 118,551, nonselective beta-, beta 1- and beta 2-selective antagonists, respectively, were constructed in rats subjected to a continuous intravenous infusion of phentolamine. The administration of each of the beta-antagonists caused a significant dose-dependent increase in mean arterial pressure (MAP). The ED50 values for the increase in MAP were found to be 3.6 +/- 0.8, 10 +/- 2.6 and 4.6 +/- 0.8 micrograms/kg for propranolol, atenolol and ICI 118,551, respectively. In the second series of experiments, a single bolus injection of a selective or nonselective beta-antagonist or saline vehicle was given to rats subjected to a continuous intravenous infusion of phentolamine. Plasma levels of A and NA were determined in the control condition, during the infusion of phentolamine and again after the injection of a beta-antagonist. The infusion of phentolamine significantly decreased MAP and increased plasma levels of A and NA.(ABSTRACT TRUNCATED AT 250 WORDS)
Tabrizchi
R
R
Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
King
K A
KA
Pang
C C
CC
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010646:Phentolamine / Q000494:pharmacology*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011412:Propanolamines; C026777:ICI 118551; D001262:Atenolol; D011433:Propranolol; D010646:Phentolamine