Angiotensin II on the release of DbetaH and atrial cyclic AMP concentrations

Abstract

The cardiac effects of angiotensin mediated by myocardial sympathetic neurons were studied in isolated rabbit left atria by comparing the effect of the peptide on field-(nerve and muscle)-stimulated and point-(muscle)-stimulated atria paced at 96 beats/min in modified oxygenated Krebs buffer at 30.degree. C. Using the indirectly acting sympathomimetic agent, tyramine, and the .beta.-adrenergic blocking agent, propranolol, evidence was obtained that angiotensin potentiated the responses to sympathetic nerve stimulation. At a concentration that maximally facilitated inotropic responses of field-stimulated atria to tyramine, angiotensin (1 .times. 10-10 M) increased atrial cyclic[c]AMP levels only during sympathetic nerve stimulation. This cAMP response was attenuated by propranolol. In concentrations greater than 3 .times. 10-11 M, angiotensin II caused a dose-dependent increase in dopamine .beta.-hydroxylase activity only in the baths of field-stimulated atria. This effect of angiotensin on atrial sympathetic neurons was antagonized competitively by saralasin (3 .times. 10-8 M). The concomitant administration of angiotensin and tyramine during field stimulation produced a greater rise in cAMP levels than was obtained with either compound alone. In concentrations which do not produce a direct inotropic response of the isolated rabbit atrium, angiotensin enhances the effects of sympathetic nerve stimulation.