The renal, cardiovascular and hormonal actions of human atrial natriuretic peptide in man; effects of indomethacin.

The renal, cardiovascular and hormonal effects of intravenous infusion of alpha-human atrial natriuretic polypeptides (alpha-hANP) at the concentrations of 0.0125, 0.025, 0.05, 0.1 microgram kg-1 min-1 for 20 min was studied in six male volunteers before and after indomethacin administration (150 mg day-1, three times daily for 3 days). Dose-dependent diuresis and natriuresis were observed in all subjects between the concentrations of 0.025 and 0.1 microgram kg-1 min-1, which were not influenced by indomethacin. Diastolic blood pressure decreased significantly (P less than 0.05) at the higher dose (0.05 microgram kg-1 min-1) of alpha-hANP, which was attenuated by indomethacin pretreatment. The plasma concentration of the immunoreactive alpha-hANP was 73.7 +/- 25 pg ml-1 on the control in subjects taking 200 mEq day-1 of sodium, and significant diuresis occurred when plasma concentration reached approximately 330.5 +/- 74.4 pg ml-1. alpha-hANP infusion caused a dose-dependent increase in cyclic GMP, no significant changes in plasma aldosterone and 18-hydroxycorticosterone, which were not influenced by indomethacin pretreatment. Plasma renin did not change in response to alpha-hANP infusion, which was significantly decreased (P less than 0.05) after indomethacin pretreatment. These results support that the renal effects of alpha-hANP may be exerted by prostaglandin-independent mechanisms. The renal effects occur at lower doses, and cardiovascular changes occur at higher doses of alpha-hANP.