ENHANCED RENAL PRODUCTION OF CYCLIC-GMP AND REDUCED FREE-WATER CLEARANCE DURING SODIUM-NITROPRUSSIDE INFUSION IN HEALTHY MAN

A 90-min intravenous infusion of the direct vasodilator sodium nitroprusside (SNP) was compared with a placebo infusion in 32 healthy control subjects in order to study the acute effects of SNP on renal haemodynamics, tubular function evaluated by the lithium clearance technique, the plasma levels of atrial natriuretic peptide (ANP), angiotensin II (Ang II), aldosterone (Aldo) and arginine vasopressin (AVP) and the tubular transport of cGMP (T(cGMP)). SNP infusion induced a significant reduction in mean arterial blood pressure (from 89.5 to 81.5 mmHg), urinary output (from 7.7 to 4.5 mi min-1), free water clearance (from 4.0 to 1.3 ml min-1) and ANP (from 3.3 to 2.5 pmol l-1) and a significant increase in heart rate (from 57 to 64 beats min-1), Ang II (from 11 to 18 pmol l-1), Aldo (from 189 to 308 pmol L-1) and in the tubular secretion of cGMP (T(cGmp) from 28.8 to 214.4 pmol min-1), (all values are medians and changes from baseline to 90 min after infusion start). Glomerular filtration rate, renal plasma flow, urinary sodium excretion, lithium clearance and plasma level of AVP were not significantly changed. It is concluded that SNP infusion in healthy subjects decreases urinary output and free water clearance without any change in sodium excretion, indicating a dissociation between the salt and water retaining effects of SNP in the early phase of treatment, probably due to an enhanced distal tubular water reabsorption of water. It is suggested that this increase in reabsorption of water in the distal parts of the nephron during SNP infusion may be mediated by an increase of cGMP production in the kidney, as indicated by the increase in T(cGMP) during the SNP infusion.