1) angiotensin II may be a more important vasoconstrictor in the developing kidney and 2) NO is a more important regulator of renal function in the developing kidney through modulation of the renin angiotensin system.
Although nitric oxide (NO) has a well-established role in regulating renal function in the adult, recent studies point to perhaps an even more critical role for NO in maintaining basal renal blood flow (RBF) and glomerular filtration rate (GFR) in the developing kidney. The immature kidney has enhanced renal hemodynamic and functional responses to stimulation and inhibition of NO synthesis when compared with the adult, and these increased responses are not mediated by prostaglandins. Increased intrarenal activity of NO in the developing kidney counter-regulates the highly activated renin angiotensin system by modulating the angiotensin II-mediated vasoconstriction of the developing renal vasculature, the angiotensin II effects on GFR, as well as renin release. Localization studies demonstrate that NO acts on neonatal RBF and stabilization of GFR through an intrarenal distribution of the synthesizing enzyme, nitric oxide synthase, that is different from that of the adult. The developing kidney is dependent on NO to maintain RBF and GFR during periods of hypoxemia, protecting against renal injury, such as acute renal failure. In summary, NO is vital in the developing kidney to maintain normal physiological function and to protect the immature kidney during pathophysiological stress.
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.
ABSTRACT. The developing mammal exhibits lower renal blood flow (RBF) and higher renal vascular resistance (RVR) than its adult counterpart. The maturational pattern of renal hemodynamics involves the synchronous increase in RBF and decrease in RVR with age. In spite of considerable investigation, the mechanisms involved in the regulation of renal hemodynamics in the developing animal remain largely unexplained. Specifically, the role of the vasodilator endotheliumderived nitric oxide (EDNO) in the regulation of developing renal hemodynamics is not known. These experiments examined the intrarenal effect on the renal hemodynamics of the developing piglet and adult pig of the EDNO competitive inhibitor N-nitro-Larginine methylester (L-NAME) at three doses (50,5, and 3 pg/kg/min). During basal conditions, the developing piglet exhibited lower RBF and higher RVR than the adult pig. All doses of intrarenal L-NAME produced significant decreases in RBF and increases in RVR in both groups. The 3-pg/kg/min L-NAME dose did not change mean arterial pressure. The developing piglet exhibited significantly greater changes at all doses. After the 50-pg/kg/min infusion, piglet RBF decreased 45% and adult pig RBF decreased 29%; piglet RVR increased 128% and adult pig RVR increased 51%. After a 5-pg/kg/min infusion, RBF
The postnatal pattern of renal endothelial nitric oxide synthase (eNOS) is unknown. The purpose of this study was to characterize eNOS expression during maturation and compare this to neuronal NOS (nNOS). The experiments measured whole kidney eNOS mRNA expression by RT-PCR and protein content by Western blot, as well as cortical and medullary protein content in piglets at selected postnatal ages and in adult pigs. Whole kidney eNOS mRNA was compared with nNOS. Whole kidney eNOS expression decreased from the newborn to its lowest at 7 days, returning by 14 days to adult levels. This eNOS mRNA pattern contrasted with nNOS, which was highest at birth, and progressively decreased to its lowest level in the adult. At birth, cortical eNOS protein was greater than medullary, contrasting with the adult pattern of equivalent levels. In conclusion eNOS is developmentally regulated during early renal maturation and may critically participate in renal function during this period. The eNOS developmental pattern differs from nNOS, suggesting that these isoforms may have different regulatory factors and functional contributions in the postnatal kidney.
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