Nitric Oxide Modulates Glomerular Filtration and Renal Blood Flow of the Newborn Rabbit

Abstract

The current study was performed in 17 anesthetized and mechanically ventilated newborn rabbits to investigate the role of nitric oxide (NO) in the regulation of basal renal function of the immature kidney. Renal blood flow and glomerular filtration rate were determined by the clearance of p-aminohippuric acid and inulin, respectively. In 9 newborn rabbits (group 1), L-NAME, a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 ± 9% and decreased the renal blood flow by 20 ± 6%. The fraction of filtration significantly increased by 8 ± 5% despite a delayed decline in glomerular filtration rate by 13 ± 5%. Mean arterial pressure and heart rate were not altered. In 8 additional newborn rabbits (group 2), L-arginine, the physiological precursor of NO synthesis, partially reversed the renal hemodynamic changes induced by L-NAME. The present results demonstrate that the decrease in NO production induced by L-NAME (1) significantly affects the renal microcirculation of the immature newborn rabbit kidney and (2) predominantly increases the postglomerular renal vascular resistance. Endogenous NO thus appears to play a major role in maintaining the basal perfusion of the immature kidney.

Reduced sensitivity of the renal vasculature to angiotensin II in young rats: the role of the angiotensin type 2 receptor

“…In further support of this conjecture, it is well established that the AT 2 R functions via a nitric oxide (NO)-mediated pathway to produce cyclic GMP and increase vasodilatation (20). Certainly, there is abundant evidence in the literature that NO plays a significantly greater role in the maintenance of hemodynamic function in the neonatal vs. adult kidney, including providing protection against the vasoconstrictor effects of AngII in the newborn (21)(22)(23)(24). Furthermore, there are reports that NO production in the renal vasculature is significantly greater in the newborn vs. adult renal vasculature under normal physiological conditions (4).…”

Neuronal nitric oxide synthase, nNOS, regulates renal hemodynamics in the postnatal developing piglet

“…Solhaug et al were the first to show an enhanced role for NO in the neonate in 1993, when intrarenal infusion of the nonspecific NOS inhibitor l-NAME into porcine caused significantly greater changes in RVR, RBF, and GFR in the newborn, than in the adult (6). This finding by Solhaug et al was confirmed in other animal models (lambs and rabbits) in which nonspecific NOS inhibition increased RVR while decreasing RBF and GFR much more significantly in neonates than in adult kidneys (4,5,8). These early studies demonstrated that the renal hemodynamics of the neonate is much more dependent on NO than that of the adult to maintain normal physiological function; however, the characteristics and exact nature of the enhanced role of NO remain unidentified.…”

“…Various studies have shown that nitric oxide (NO) plays a much more pronounced role in the neonate's hemodynamic state, as compared with the adult's, and NO counterbalances the highly activated reninangiotensin system (RAS), protecting the immature kidney from the deleterious effects of adverse perinatal events that lead to vasomotor acute renal failure (2)(3)(4)(5)(6)(7). The immature renal vasculature is highly responsive to intrarenal NO stimulation with acetylcholine and NO inhibition with the nonselective nitric oxide synthase (NOS) inhibitor L-nitro-arginine methyl ester (l-NAME) (8)(9)(10)(11), producing significantly greater increases in RVR and decreases in RBF and GFR in the immature kidney, as compared with the adult.…”

Beneficial effect of insulin-like growth factor-1 on hypoxemic renal dysfunction in the newborn rabbit

“…Our group previously demonstrated that L-NAME administration was accompanied by a worsening of the hypoxemia-induced renal vasoconstriction, suggesting that endogenous NO is functionally present in the immature kidney and that NOS activity is maintained during acute hypoxemia [6]. Moreover, endogenous NO maintains neonatal basal renal perfusion mainly through postglomerular renal vascular resistance [37].…”