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)