l‐ARGININE INFUSION INDUCES HYPOTENSION AND DIURESIS/NATRIURESIS WITH CONCOMITANT INCREASED URINARY EXCRETION OF NITRITE/NITRATE AND CYCLIC GMP IN HUMANS

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Abstract
SUMMARY: 1. The vascular endothelium produces endothelium‐derived relaxing factor (EDRF) or nitric oxide (NO), which exerts vasodilation through cyclic guanosine monophosphate (cGMP) as a second messenger. To determine whether EDRF has any vasodilating and natriuretic action in man, the present study examined the effects of l‐arginine (l‐Arg), a substrate for NO, on the responses of mean blood pressure (MBP) and heart rate (HR); plasma concentrations of cGMP, atrial natriuretic factor (ANF) and nitrite/nitrate (NOx); urinary excretion of sodium, cGMP and NOx; and urinary flow in eight normal male subjects. These parameters were compared with those following saline infusion in the same subjects. Clearance of para‐aminohippuric acid (PAH) and inulin was studied in five normal subjects.2. Infusion of l‐Arg (30 g) caused a significant fall in MBP (–8 mmHg) with a concomitant rise in HR (10 beats/min), while saline infusion had no effects on these parameters.3. Neither l‐Arg nor saline infusion caused appreciable changes in plasma concentrations of ANF or NOx. Plasma cGMP concentrations increased significantly during (1.7‐fold) and after (1.9‐fold) l‐Arg infusion, but only slightly (1.3‐fold) during saline infusion.4. Urine flow increased more remarkably following l‐Arg infusion than that following saline infusion. Remarkable increases in urinary excretion of sodium and fractional excretion of sodium were observed after l‐Arg infusion compared with those after saline infusion. Natriuresis was associated with enhanced urinary excretion of cGMP and Nox. Urinary NOx excretion showed positive correlations with urinary flow (r= 0.69, P < 0.001) and with urinary cGMP excretion (r= 0.60, P < 0.01). PAH clearance showed significant increase by l‐Arg infusion, while no significant change of inulin clearance was observed.5. These date suggest that infusion of l‐Arg causes hypotension and diuresis/natriuresis associated with increase in renal plasma flow, possibly via the formation of endogenous EDRF in man.