Antihypertensive and hypotensive effects of atrial natriuretic factor in men.

Abstract

Synthetic atrial natriuretic factor (ANF) was administered in ascending doses (0.03, 0.20, 0.45 .mu.g/kg/min) to eight mildly essential hypertensive men on high (200 mEq/day) or low (10 mEq/day) sodium diets. Responses of blood pressure, heart rate, urinary volume and electrolyte excretion, renin, and aldosterone were measured. For the entire group, ANF lowered blood pressure and increased heart rate during the 0.20 and 0.45 .mu.g/kg/min infusions, and the antihypertensive effect of the peptide persisted for at least 2 hours after the infusions ended. Four patients (2 at 0.20 .mu.g/kg/min and 2 at 0.45 .mu.g/kg/min) experienced sudden bradycardia and hypotension at the end of or shortly after completion of ANF infusion. Renal excretion of water, sodium, chloride, calcium, and phosphorus increased in a dose-dependent fashion in response to infused ANF. Patients on the 200 mEq/day sodium diet had greater increases in urinary volume (11.1 .+-. 2.8 vs. 3.0 .+-. 2.0 ml/min; p < 0.05), sodium (870 .+-. 134 vs 303 .+-. 27 .mu.Eq/min; p < 0.05), and chloride (801 .+-. 135 vs 176 .+-. 75 .mu.Eq/min; p < 0.02) compared with patients on the low sodium diet. The apparent direct suppressive effect of a 0.03 .mu.g/kg/min infusion of ANF on renin and aldosterone levels was overcome at higher doses by counterregulation provoked by the depressor action. Renin was slightly (-12%) suppressed during the 0.03 .mu.g/kg/min infusion of ANF but increased at the 0.20 (+50%) and 0.45 .mu.g/kg/min (+90%; p < 0.03) rates. Aldosterone declined significantly during the 0.03 .mu.g/kg/min infusion (-45%; p < 0.01) of ANF but not during the two higher dose infusions. There were no significant differences in renin and aldosterone responses for the 200 mEq/day and 10 mEq/day sodium diets. We conclude that the depressor action of 1-hour infusions of very high doses of synthetic ANF in essential hypertensive men is associated with a high risk of late hypotension. Dietary sodium restriction diminishes the peak natriuretic effect of infused ANF but does not significantly affect responses of blood pressure, heart rate, renin, or aldosterone.