The acute response of plasma norepinephrine, renin activity, and arginine vasopressin to short-term nitroprusside and nitroprusside withdrawal in patients with congestive heart failure

Abstract

Activation of the sympathetic nervous system, manifested by an increase in heart rate and circulating plasma norepinephrine, can occur in normal subjects when they are given vasodilators. The extent to which this activation occurs in patients with congestive heart failure (CHF) and whether this activation could account for the hemodynamic rebound sometimes observed following abrupt withdrawal of nitroprusside in such patients are unclear. We prospectively and retrospectively studied the effects of nitroprusside on plasma norepinephrine in 38 patients with CHF to determine if acute vasodilator therapy activates this vasoconstrictor system during or following such treatment. Thirty-six of these patients also had plasma renin activity (PRA) measured and plasma arginine vasopressin was measured in 12 patients. Baseline supine plasma norepinephrine (714 ± 72 pg/ml, ± SEM), PRA (15 ± 2 ng/ml/hr), and arginine vasopressin (10 ± 1 pg/ml) were increased at least twofold in the CHF patients. Nitroprusside (96 ± 11 μg/min) was infused for 63 ± 5 minutes after achieving an optimal hemodynamic response: cardiac index increased (2.01 ± 0.08 to 2.67 ± 0.1 L/min/m 2, p < 0.001), pulmonary artery wedge pressure decreased (25 ± 1 to 16 ± 1 mm Hg, p < 0.001), mean arterial pressure decreased (83 ± 1 to 72 ± 1 mm Hg, p < 0.001), and heart rate was unchanged. Plasma norepinephrine (632 ± 43 pg/ml), PRA (18 ± 3 ng/ml/hr), and arginine vasopressin (11 ± 1 pg/ml) did not change significantly for the group during peak effect of the vasodilator. Nitroprusside was abruptly stopped and 36 ± 2 minutes later there was no significant change for the group in plasma norepinephrine (755 ± 72 pg/ml), PRA (18 ± 3 ng/ml/hr), or arginine vasopressin (11 ± 1 pg/ml). There was no hemodynamic rebound for the group following nitroprusside withdrawal, although some individual patients did show a rebound increase in systemic vascular resistance. In these individuals there was no consistent relationship between changes in plasma norepinephrine, renin activity, and arginine vasopressin and the observed increase in the systemic vascular resistance. On the basis of these data we conclude that short-term nitroprusside therapy for CHF does not consistently alter plasma norepinephrine, PRA, or plasma arginine vasopressin concentration. The rebound in systemic vascular resistance that may be observed in individual patients when nitroprusside is abruptly withdrawn does not appear to be modulated by activation of the sympathetic nervous system, the renin-angiotensin system, or arginine vasopressin.