A comparison of the cardiovascular actions of four adrenergic β-receptor blocking agents in resting, conscious dogs

Abstract

The present study was undertaken to investigate the effect of blockade of adrenergic β-receptors on resting hemodynamics in conscious dogs. Contrary to the findings in anesthetized animals, in which the activity of the autonomic nervous system is markedly altered, propranolol and MJ 1999 had little effect on heart rate, cardiac output, and left ventricular work. These two drugs were also equipotent in blocking the cardiovascular effects induced by isoprenaline. H 56 28 and I.C.I. 50172 have been shown to possess intrinsic sympathomimetic activity; in the present experiments H 56 28 also increased heart rate and decreased total peripheral resistance. I.C.I. 50172 did not alter the systemic hemodynamics in conscious dogs. H 56 28 had comparable activity to propranolol and MJ 1999 in blocking the response to isoprenaline, while I.C.I. 50172 was less potent. In contrast with the earlier observations that β-receptor blocking agents markedly decrease coronary flow in anesthetized animals, propranolol, MJ 1999, and H 56 28 had practically no effect on resting coronary circulation in conscious dogs. All three drugs increased coronary resistance and were almost equipotent in blocking the effect of isoprenaline on coronary hemodynamics. I.C.I. 50172 had a biphasic dose-dependent effect: the coronary flow was increased by the smallest dose and decreased after the largest one. This compound had no effect on late diastolic resistance and was less potent than the other three drugs in antagonizing the coronary changes induced by isoprenaline. The present observations indicate that β-receptor blocking agents have little effect on the coronary circulation and systemic hemodynamics, and suggest that it could be misleading to extrapolate the findings in anesthetized dogs to man.