Interrelation of coronary effects of atrial natriuretic peptide and the renin-angiotensin system in the isolated perfused rat heart

Abstract

The coronary vascular effect of atrial natriuretic peptide is controversial: Coronary vasodilator as well as constrictor effects have been reported. The controversy may originate from interference of atrial natriuretic peptide with the renin-angiotensin system and/or tachyphylaxis of the effect of atrial natriuretic peptide. The effect of alpha-human atrial natriuretic peptide bolus application on changes of coronary flow was examined in the isolated, constant-pressure perfused rat heart. Six groups were considered: (1) control group; groups in which the renin-angiotensin system was modulated by pretreatment with continuous infusion of: (2) angiotensin II, (3) the angiotensin converting enzyme inhibitor captopril (4) the angiotensin II receptor blocker saralasin; and groups in which tachyphylaxis was examined by pretreatment with ANP, (5) as continuous infusion and (6) as bolus application. First, in control hearts, dose-response curves were obtained for single ANP dosages of 1-100 nmol. The effect of high dosages (40 and 100 nmol) was biphasic, with an initial vasodilator and subsequent long-lasting vasoconstrictor component. Hearts in which coronary flow was reduced by approximately 18% through continuous angiotensin II infusion showed an enhanced early vasodilator response after ANP administration, whereas the vasoconstrictor effect was no longer observable. Angiotensin converting enzyme inhibition and angiotensin II receptor blockade reduced the vasodilator effect of ANP. In addition, saralasin nearly abolished ANP-induced vasoconstriction, whereas vasoconstriction was unaltered by pretreatment with captopril. Captopril or saralasin alone did not change coronary flow, heart rate and left ventricular developed pressure. In groups (5) and (6). ANP bolus application showed significantly reduced vasomotor activity. We conclude that in the isolated rat heart. ANP has a biphasic effect with early vasodilation and late vasoconstriction. Both effects can be modulated by inhibition of the renin-angiotensin system at different levels indicating that vasomotor ANP effects result from interaction of ANP with the local renin-angiotensin system. ANP effects can be markedly reduced by tachyphylaxis.