L-arginine infusion induces hypotension and diuresis/natriuresis with concomitant increased urinary excretion of nitrite/nitrate and cyclic GMP in humans.
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 less than 0.001) and with urinary cGMP excretion (r = 0.60, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Kanno
K
K
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Hirata
Y
Y
Emori
T
T
Ohta
K
K
Eguchi
S
S
Imai
T
T
Marumo
F
F
D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000097:blood / Q000652:urine*; D004231:Diuresis / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D009566:Nitrates / Q000097:blood / Q000652:urine; D009573:Nitrites / Q000097:blood / Q000652:urine; D009589:Nitrogen Oxides / Q000097:blood / Q000652:urine*; D014664:Vasodilation
D009566:Nitrates; D009573:Nitrites; D009589:Nitrogen Oxides; D001120:Arginine; D006152:Cyclic GMP