Volume expansion during NOS substrate donation with l-arginine: regulatory offsetting of renal response?

Abstract

The responses to infusion of nitric oxide synthase substrate (l-arginine 3 mg · kg−1 · min−1) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. l-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 ± 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 ± 0.0 to 0.7 ± 0.1 ml/min). Volume expansion increased arterial blood pressure (102 ± 3 to 114 ± 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 ± 31 μmol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 ± 1.7 to 1.6 ± 0.3 pg/ml). Combined volume expansion and l-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 ± 23 μmol/min at plasma ANG II levels of 3.0 ± 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, l-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus l-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.