Effects of selective (beta-1 and beta-2) and nonselective beta adrenoceptor antagonists on the cardiovascular and metabolic responses to isoproterenol: comparison with ICI 141,292.

Six groups of four dogs were studied under pentobarbital anesthesia. Plasma levels of free fatty acids (FFA), glucose, insulin and lactate were measured after four challenges with isoproterenol (0.125 micrograms/kg/min i.v. for 10 min). In control animals, infusion of isoproterenol elevated plasma FFA, glucose, insulin and lactate, raised heart rate and lowered diastolic blood pressure. Propranolol lowered resting heart rate and blocked all the isoproterenol-induced responses. Atenolol (beta-1-selective antagonist) slowed resting heart rate and blocked FFA and heart rate responses. ICI 118,551 (beta-2-selective antagonist) blocked the glucose, insulin and lactate responses and the fall in diastolic blood pressure. Selectivity was lost at higher doses. ICI 141,292 (potent beta-1-selective antagonist and modest partial agonist) exhibited beta-1-selective blockade against both cardiovascular (heart rate) and metabolic (FFA) receptors. Partial agonist activity was also beta-1-selective, but there was no evidence of agonist activity at the metabolic receptors.