Cardiac adenylate cyclase activity in relation to beta-adrenergic responses

Abstract

The effect of beta-adrenergic receptor agonists (isoproterenol, hexoprenaline, salbutamol) on the adenylate cyclase activity and some functional parameters of the atrial and ventricular myocardium of the rabbit was investigated. The influence of isoproterenol was studied also in the presence of beta-adrenergic receptor antagonists (practolol, pindolol). The beta-adrenergic stimulants had a similar decreasing order of relative potency (isoproterenol > hexoprenaline > salbutamol) in stimulating atrial or ventricular adenylate cyclase, in increasing atrial or ventricular contractility, spontaneous atrial rate, the maximum driving frequency of the ventricular myocardium and in reducing ventricular electrical threshold. Isoproterenol proved to be the most potent adrenergic agonist also in decreasing atrial electrical threshold, but in this respect salbutamol was slightly more active than hexoprenaline. Practolol and pindolol inhibited the effects of isoproterenol on adenylate cyclase activity and also on the functional parameters. Some statistical correlation was also found between the adrenergically-induced rise in cyclic AMP levels and the corresponding changes in the physiological functions of the myocardium. However, concentrations of the studied adrenergic agonists required to equally activate adenylate cyclase produced significantly different effects on the functional parameters, and analysis of the results has shown that the observed correlations reflect, at least in part, parallel processes rather than an exclusive cause and effect relationship.