Physiological effects of synthetic atrial natriuretic factor in normal conscious dogs

The objective of this study was to examine the integrative physiologic effects of atrial natriuretic factor (ANF). Synthetic 99-126 ANF was administered to 6 normal conscious dogs as two consecutive infusions (0.02 and 0.1 microgram/kg/min respectively) each over 30 min: each infusion was preceded by a priming dose of 1 microgram/kg. With the first infusion, mean arterial pressure declined from 113 +/- 2 to 103 +/- 4 mmHg, pulmonary capillary wedge pressure declined from 9.6 +/- 0.5 to 7.2 +/- 0.7 mmHg and right atrial pressure declined from 9.8 +/- 0.4 to 8.0 +/- 0.7 mmHg (all p less than 0.05). No change in heart rate was seen. Despite very high plasma ANF concentrations, no further decline in arterial or central filling pressures were seen in the second infusion. In contrast, cardiac output declined progressively from 3.8 +/- 0.2 to 2.8 +/- 0.21/min (p less than 0.01) by the end of second infusion. Plasma renin activity declined from 2.2 +/- 0.7 to 0.9 +/- 0.3 ng/ml/hr (p less than 0.05) while plasma norepinephrine remained unchanged. Urine output and sodium excretion increased in a dose dependent manner. The diverse time course of the hemodynamic, renal and neuroendocrine effects suggests these effects of ANF are mediated by different mechanisms. Furthermore, the failure of heart rate and plasma norepinephrine to increase despite a significant decline in blood pressure and cardiac output suggests ANF may have a depressant effect on the sympathetic nervous system.