Effect of L-arginine infusion in normotensive subjects with and without a family history of hypertension

Background. Experimental studies have shown that nitric oxide (NO) generati on in the kidney from L-arginine particles pates in the regulation of renal function. Our purpose was to study the effect of infusion of L-arginine (1 , 5, and 10 mg/kg/min) on blood pressure (BP), renal bemodynamics, and urin ary excretion of sodium and albumin in normotensive subjects with a family history of either severe hypertension (FHSH, N = 17) or mild hypertension ( FHMH, N = 20) and in control subjects (N = 18) without a hereditary predisp osition for hypertension. Methods. The glomerular filtration rate (GFR) and renal plasma flow (RPF) w ere measured by renal clearances of Cr-51 ethylenediaminetetraacetic acid a nd paramino-hippurate. Renal tubular reabsorption of sodium was estimated b y lithium clearance. To evaluate the effect of L-arginine infusion on the L -arginine/NO pathway, we measured the NO-metabolite nitrate in plasma, and urinary excretion of cGMP, the second messenger of NO. The derivative at an L-arginine dose of 7.5 mg/kg/min was used as a measure of sensitivity to L -arginine. Results. There was no difference in baseline systolic BP between the groups . but diastolic BP was significantly higher in FHSH compared with control s ubjects (P < 0.05). L-arginine caused a significant increase in urine flow, urinary excretion of albumin and sodium, and lithium clearance in all grou ps. FHSH showed a significantly decreased sensitivity to L-arginine with re spect to urine flow rate (P = 0029) compared with FHMH and control subjects . L-arginine caused a significant decrease in the GFR in FHSH (P < 0.02) an d control subjects (P < 0.001), but in FHMH, the decrease did not reach sta tistical significance (P = 0.097). There was no difference in sensitivity t o L-arginine with respect to BP, RPF, or GFR between the three groups. In a ll patients, there was a significant positive relationship between Delta ur ine flow rate or Delta urinary sodium excretion and Delta GFR during infusi on of L-arginine (P = 0.003 and P = 0.03. respectively). Plasma nitrate and urinary cGMP decreased in all groups during the L-arginine infusion. Conclusion. L-Arginine infusion in normotensive subjects caused an enhanced urine flow rate and urinary sodium and albumin excretion and a slight redu ction in GFR. The effect of L-arginine on the urine flow rate was significa ntly less pronounced in subjects with a family history of severe hypertensi on, which may indicate a tubular disturbance in hypertension.