Effects of alpha-human atrial natriuretic peptide in guinea-pig isolated heart

The aim of the present investigation has been to ascertain whether or not atrial natriuretic peptides (ANP) can exert a direct effect on myocardial contractility. Alpha-human ANP (alpha-hANP) concentrations ranging from 1 pM to 50 nM have been used to perfuse guinea-pig isolated hearts in a non-recirculating Langendorff apparatus. A dual concentration-related effect has been induced by alpha-hANP on myocardial function. A maximal increase of +LV dP/dtmax (+56%; P < 0.001) has been observed when guinea-pig hearts were perfused with 100 pM alpha-hANP, whereas a 25% decrease (P < 0.01) occurred with 50 nM alpha-hANP. Similar effects have also been induced by alpha-hANP on the coronary flow rate (CFR). A significant CFR increase (maximal at 10 pM alpha-hANP) was induced by picomolar concentrations of alpha-hANP, whereas a progressive decrease, which was maximal (-28%; P < 0.01) at 50 nM alpha-hANP, was observed with nanomolar concentrations of the peptide. No effects have been observed on heart rate. These results suggest that ANP has direct effects on both vascular and myocardial muscle cells. Coronary vasoconstriction induced by nanomolar concentrations of ANP can contribute to the cardiodepression, whereas ANP in picomolar concentrations can induce a coronary vasodilation which is not coupled with the enhanced myocardial contractility. The latter is the likely expression of a direct effect of the peptide on myocardial function.