Ontogeny of neuronal nitric oxide synthase, NOS I, in the developing porcine kidney

Abstract

To determine if the developing kidney differs from the adult in the expression of the neuronal nitric oxide synthase, NOS I, these experiments measured mRNA gene expression by RNase protection assay and protein content by Western blot of NOS I in piglets at ages newborn and 3, 7, 10, 14, and 21 days and adult pigs. Whole kidney NOS I mRNA was greatest at birth and decreased progressively during renal maturation to adult levels. NOS I protein content paralleled this developmental pattern. Cortical NOS I protein was equivalent in newborn and 14-day-old piglets and was greater at both ages than the adult. Medullary NOS I protein was relatively greater than cortical in both immature ages and decreased from a peak at birth to adult levels. We conclude the following. 1) During postnatal maturation, renal NOS I mRNA and protein content show a pattern that is developmentally regulated. 2) This developmental pattern of NOS I after birth may, in part, contribute to the enhanced functional role of NO during renal maturation.

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

“…An alternative explanation is that there is an age-dependent effect of endogenously produced NO on net filtration pressure through its vasodilatory effects on afferent arteriolar tone. This premise is supported by an age-dependent distribution of renal nNOS mRNA gene expression and localization (11,35,37). Furthermore, Kullaprawithaya et al (21), using elegant laser capture microdissection techniques, recently reported that macula densa nNOS mRNA gene expression is greater in newborn piglets than older pigs.…”

“…Furthermore, the renal distribution of NOS is also developmentally regulated. For example, Solhaug et al (35) measured renal nNOS mRNA gene expression in piglets and adult pigs and observed a greater nNOS mRNA in immature compared with mature kidneys. In guinea pigs, Thompson and Weiner (37) found that NOS activity increased during fetal life to reach maximal levels in the newborn kidney, decreasing thereafter.…”

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

“…During the newborn's period of increased NO production, eNOS expression is minimally detectable, with protein levels sevenfold less than what is observed in the adult (20). However, nNOS expression in whole-kidney models and in microdissected preglomerular resistance vessels is significantly enhanced in the newborn and strongly suggests that the nNOS isoform, and not eNOS, is the major NOS isoform contributing NO to the newborn's renal hemodynamic state (3,19,20).…”

“…NO is known to inhibit cyclic adenosine monophosphate degradation through cyclic GMP-mediated mechanisms, thereby stimulating renin secretion, whereas cellular calcium influx and protein kinase K activation inhibit renin release (36 (3,11,19). In studies by Ratliff et al, it was demonstrated that NO production in the preglomerular resistance vasculature is threefold higher in the newborn than in the adult (19,20).…”

“…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.…”