Glomerular and tubular responses toN G-nitro-l-arginine methyl ester are age dependent in conscious lambs

Abstract

The present experiments were carried out to investigate the role of endogenously produced NO in modulating renal function during postnatal maturation under physiological conditions. In conscious, chronically instrumented lambs aged ∼1 ( n= 8) and ∼6 wk ( n = 8) of postnatal life, various parameters of glomerular and tubular function were measured for 1 h before and 1 h after intravenous injection of 20 mg/kg of N G-nitro-l-arginine methyl ester (l-NAME; experiment 1) or its inactive isomerd-NAME ( experiment 2). After administration ofl-NAME to 1-wk-old lambs, glomerular filtration rate (GFR) and filtration factor (FF) decreased by ∼50% at 20 min, remaining decreased at 60 min. In 6-wk-old lambs, GFR and FF remained constant after l-NAME. Proximal fractional Na+reabsorption decreased after l-NAME administration to lambs aged 6 wk, resulting in a prompt natriuresis; this was sustained for 60 min. There were no effects of l-NAME on proximal fractional Na+ reabsorption in 1-wk-old lambs. In 6-wk-old lambs, urinary flow rate increased by ∼500%, free water clearance increased by ∼50%, and urinary osmolality decreased by ∼60% afterl-NAME administration; no effects on these variables were measured in 1-wk-old lambs. The diuresis after l-NAME administration to 6-wk-old lambs was unaccompanied by any changes in plasma levels of arginine vasopressin. There were no effects ofd-NAME on any of the measured variables. We conclude that endogenously produced nitric oxide modulates glomerular and tubular function in an age-dependent manner.