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) generation in the kidney from L-arginine participates 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 hemodynamics, and urinary 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 predisposition for hypertension.


METHODS
The glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by renal clearances of Cr51 ethylenediaminetetraacetic acid and paramino-hippurate. Renal tubular reabsorption of sodium was estimated by 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 subjects (P < 0.05). L-arginine caused a significant increase in urine flow, urinary excretion of albumin and sodium, and lithium clearance in all groups. FHSH showed a significantly decreased sensitivity to L-arginine with respect 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) and control subjects (P < 0.001), but in FHMH, the decrease did not reach statistical significance (P = 0.097). There was no difference in sensitivity to L-arginine with respect to BP, RPF, or GFR between the three groups. In all patients, there was a significant positive relationship between Delta urine flow rate or Delta urinary sodium excretion and Delta GFR during infusion 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.


CONCLUSIONS
L-Arginine infusion in normotensive subjects caused an enhanced urine flow rate and urinary sodium and albumin excretion and a slight reduction in GFR. The effect of L-arginine on the urine flow rate was significantly less pronounced in subjects with a family history of severe hypertension, which may indicate a tubular disturbance in hypertension.
Herlitz
H
H
Department of Nephrology, Sahlgrenska University Hospital, Göteborg, Sweden. Hans.Herlitz@medic.gu.se
Jungersten
L U
LU
Wikstrand
J
J
Widgren
B R
BR
D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism
D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D012083:Renin