Enhancement of coronary conductance by alpha-human atrial natriuretic polypeptide without effects on myocardial contractility

The effect of synthetic human atrial 28-amino acid peptide (alpha-human atrial natriuretic polypeptide, alpha-hANP) on coronary circulation and cardiac functions was examined in open-chest dogs. Intravenous injection of alpha-hANP increased coronary and systemic conductance, and coronary and aortic blood flow with a significant fall in blood pressure. Continuous infusion of alpha-hANP into the left anterior descending coronary artery (LAD) increased LAD blood flow in a dose-dependent manner. The linear regression analysis revealed the relationship of logit (changes in mean coronary conductance (delta MCC] = 1.45 x log (coronary plasma concentration of alpha-hANP) + 7.51 (r = 0.87, n = 29). REC50 of alpha-hANP was 5.1 microM, where REC50 was the concentration to increase MCC to a half maximum MCC during reactive hyperemia after a 30-s coronary occlusion. alpha-hANP increased coronary conductance with no changes of myocardial oxygen consumption (MVO2) when blood pressure remained constant. Indices of myocardial contractility measured with a strain gauge arch, myocardial force (F), max dF/dt and LV max dp/dt, were not altered by either bolus intravenous injection or continuous intracoronary infusion of alpha-hANP. These results indicated a direct increase by alpha-hANP of coronary and systemic vascular conductance.