EFFECTS OF SELECTIVE (BETA-1 AND BETA-2) AND NON-SELECTIVE BETA-ADRENOCEPTOR ANTAGONISTS ON THE CARDIOVASCULAR AND METABOLIC RESPONSES TO ISOPROTERENOL - COMPARISON WITH ICI-141,292

  • 1 January 1983
    • journal article
    • research article
    • Vol. 226  (1) , 211-216
Abstract
Six groups of 4 dogs were studied under pentobarbital anesthesia. Plasma levels of free fatty acids (FFA), glucose, insulin and lactate were measured after 4 challenges with isoproterenol (0.125 .mu.g/kg per 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 respones. Atenolol (.beta.-selective antagonist) slowed resting heart rate and blocked FFA and heart rate responses. ICI 118,551 [erythro-DL-1-(7-methylindan-4-yloxy)-3-isopropylamino-butan-2-ol] (.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.-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.