Abstract
Nitric oxide (NO), produced by nitric oxide synthase (NOS), critically counteracts angiotensin-II-enhanced vascular resistance in the immature kidney, perhaps due to the developmental regulation of NOS expression and function in the postnatal preglomerular resistance vessels (PRV). Our experiments measured the messenger ribonucleic acid (mRNA) gene expression of neuronal NOS (nNOS), endothelial NOS (eNOS), and components of the renin–angiotensin system (renin, AT1 and AT2 receptors), by real-time RT-PCR, as well as NOS enzymatic activity by citrulline assay in PRVs (afferent, interlobular, and arcuate arterioles) obtained from swine ages newborn, 7 and 21 days, and adult. NOS enzymatic activity was upregulated in PRVs immediately after birth but decreased to adult levels with maturation. Neuronal NOS, renin, and AT2 receptor expression in PRVs were upregulated in the newborn and decreased with age to lowest levels in the adult. In contrast, eNOS and AT1 receptor expression were downregulated at birth but increased to the highest levels in the adult. Upregulated NOS enzymatic activity in newborn PRVs supports the critical neonatal role for NO renal vascular vasodilation. Upregulated nNOS gene expression, concomitant with downregulated eNOS gene expression in neonatal PRVs, suggests that the nNOS isoform may be responsible for counteracting angiotensin II increased vascular resistance in immature porcine PRVs.
Similar content being viewed by others
References
Ballèvre L, Thonney M, Guignard JP (1994) Role of nitric oxide in regulating renal hemodynamics in newborn rabbits. Pediatr Nephrol 8:C42
Toth-Heyn P, Drukker A, Guignard JP (2000) The stressed neonatal kidney: from pathophysiology to clinical management of neonatal vasomotor nephropathy. Pediatr Nephrol 14:227–239
Norman ME, Asadi FK (1979) A prospective study of acute renal failure in the newborn infant. Pediatrics 63:475–479
Chevalier RL, Campbell F, Brenbridge AN (1984) Prognostics factors neonatal acute renal failure. Pediatrics 74:265–272
Stapleton FB, Jones DP, Green RS (1987) Acute renal failure in neonates: incidence, etiology and outcome. Pediatr Nephrol 1:314–320
Sedman AB, Kershaw DB, Bunchman TE (1995) Recognition and management of angiotensin converting enzyme inhibitor fetopathy. Pediatr Nephrol 9:382–385
Rubin ML (1949) Maturation of renal function in childhood: clearance studies. Clin Invest 28:1144
Gruskin AB, Edelman CM Jr, Yuan S (1970) Maturational changes in renal blood flow in piglets. Pediatr Res 4:7–13
Kleinman LI, Lubbe RJ (1972) Factors affecting the maturation of glomerular filtration rate and renal plasma flow in the newborn dog. J Physiol 223:395–409
Pezzati M, Danesi G, Pozzessere A, Cosenza EB, Rubaltelli FF (1998) Renal blood flow velocity in preterm and term neonates during the forth day of life: changes in relation to gestational age and birth rate. Biol Neonate 73:19–23
Pokharel RP, Uetani Y, Tsuneishi S, Nakamura H (1997) Neonatal renal blood flow velocities using color doppler ultrasonography. Kobe J Med Sci 43:1–12
Fawer CL, Torrado A, Guignard JP (1979) Maturation of renal function in full-term and premature neonates. Helv Paediatr Acta 34:11–21
Calcagno PL, Rubin ML (1963) Renal extraction of para-amminohippurate in infants and children. J Clin Invest 42:1632
Aperia A, Broberger O, Herin P (1974) Maturation changes in glomerular perfusion rate and glomerular filtration rate in lambs. Pediatr Res 8:758–765
Jose PA, Logan AG, Slotkoff LM, Lilienfield LS, Calcagno PL, Eisner GM (1971) Intrarenal blood flow distribution in canine puppies. Pediatr Res 5:335–344
Olbing H, Blaufox MD, Aschinberg LC, Silkalns GI, Bernstein J, Spitzer A, Edelmann CM Jr (1973) Postnatal changes in renal glomerular blood flow distribution in puppies. J Clin Invest 52:2885–2895
Robillard JE, Nakamura KT (1988) Neurohormonal regulation of renal function during development. Am J Physiol 254:F771–F779
Aschinberg LC, Goldsmith DI, Olbing H, Spitzer A, Edelmann CM Jr, Blaufox D (1975) Neonatal changes in renal blood flow distribution in puppies. Am J Physiol 228:1453–1461
Horster M, Valtin H (1971) Postnatal development of renal function: micropuncture and clearance studies in the dog. J Clin Invest 50:779–795
Solhaug MJ, Ballevre LD, Guignard JP, Granger JP, Adelman RD (1996) Nitric oxide in the developing kidney. Pediatr Nephrol 10:529–539
Solhaug MJ, Wallace MR, Granger JP (1996) Nitric oxide and angiotensin II regulation of renal hemodynamics in the developing piglet. Pediatr Res 39:527–533
Guignard JP, Gouyon JB, John EG (1991) Vasoactive factors in the immature kidney. Pediatr Nephrol 5:443–446
Osborn JL, Hook JB, Bailie MD (1980) Regulation of plasma renin in developing piglets. Dev Pharmacol Ther 1:217–228
Pelayo JC, Eisner GM, Jose PA (1981) The ontogeny of the renin-angiotensin system. Clin Perinatol 8:347–359
Sulyok E, Nemeth M, Tenyi I, Csaba I, Gyory E, Ertl T, Varga F (1979) Postnatal development of the renin-angiotensin-aldosterone system, RAAS, in relation to electrolyte balance in premature infants. Pediatr Res 13:817–820
Wallace KB (1980) Postnatal development of the renin-angiotensin system in rats. Am J Physiol 238:R432–R437
Gomez RA (1998) Role of angiotensin in renal vascular development. Kidney Int Suppl 67:S12–S16
Gomez RA, Lynch KR, Chevalier RL, Wilfong N, Everett A, Carey RM, Peach MJ (1988) Renin and angiotensinogen gene expression in maturing rat kidney. Am J Physiol 254:F582–F587
Gomez RA, Lynch KR, Sturgill BC, Elwood JP, Chevalier RL, Carey RM, Peach MJ (1989) Distribution of renin mRNA and its protein in the developing kidney. Am J Physiol 257:F850–F858
Ciuffo GM, Viswanathan M, Seltzer AM, Tsutsumi K, Saavedra JM (1993) Glomerular angiotensin II receptor subtypes during development. Am J Physiol 265:F264–F271
Matsusaka T, Miyazaki Y, Ichikawa I (2002) The renin angiotensin system and kidney development. Annu Rev Physiol 64:551–561
Shanmugam S, Lenkei ZG, Gasc JM, Corvol PL, Llorens-Cortes CM (1995) Ontogeny of angiotensin II type 2 (AT2) receptor mRNA in the rat. Kidney Int 47:1095–1100
Tufro-McReddie A, Gomez RA (1993) Ontogeny of the renin-angiotensin system. Semin Nephrol 13:519–530
Yoo KH, Norwood VF, el Dahr SS, Yosipiv I, Chevalier RL (1997) Regulation of angiotensin II AT1 and AT2 receptors in neonatal ureteral obstruction. Am J Physiol 273:R503–R509
Solhaug MJ, Wallace MR, Granger JP (1993) Endothelium-derived nitric oxide regulates renal hemodynamics in the developing piglet. Pediatr Res 34:750–754
Simeoni U, Helwig JJ (1997) Nitric oxide (NO) and normal and pathologic renal development. Pediatr Med Chir 19:313–315
Sener A, Smith FG (2001) Renal hemodynamic effects of L-NAME during postnatal maturation in conscious lambs. Pediatr Nephrol 16:868–873
Solhaug MJ, Dong XQ, Adelman RD, Dong KW (2000) Ontogeny of neuronal nitric oxide synthase, NOS I, in the developing porcine kidney. Am J Physiol Regul Integr Comp Physiol 278:R1453–R1459
Solhaug MJ, Kullaprawithaya U, Dong XQ, Dong KW (2001) Expression of endothelial nitric oxide synthase in the postnatal developing porcine kidney. Am J Physiol Regul Integr Comp Physiol 280:R1269–R1275
Han KH, Lim JM, Kim WY, Kim H, Madsen KM, Kim J (2005) Expression of endothelial nitric oxide synthase in developing rat kidney. Am J Physiol Renal Physiol 288:F694–F702
Bachmann S, Bosse HM, Mundel P (1995) Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney. Am J Physiol 268:F885–F898
Mattson DL, Wu F (2000) Nitric oxide synthase activity and isoforms in rat renal vasculature. Hypertension 35:337–341
Terada Y, Tomita K, Nonoguchi H, Marumo F (1992) Polymerase chain reaction localization of constitutive nitric oxide synthase and soluble guanylate cyclase messenger RNAs in microdissected rat nephron segments. J Clin Invest 90:659–665
Ujiie K, Yuen J, Hogarth L, Danziger R, Star RA (1994) Localization and regulation of endothelial NO synthase mRNA expression in rat kidney. Am J Physiol 267:F296–F302
Kone BC (1999) Localization and regulation of nitric oxide synthase isoforms in the kidney. Semin Nephrol 19:230–241
Pelayo JC, Mobilia M, Tjio S, Singh R, Nakamoto JM, Van Dop C (1994) A method for isolation of rat renal microvessels and mRNA localization. Am J Physiol Renal Physiol 267:F497–F503
Bosse HM, Bohm R, Resch S, Bachmann S (1995) Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli. Am J Physiol 269:F793–F805
Gabbai FB, Blantz RC (2002) Role of nitric oxide in renal hemodynamics. Semin Nephrol 19:242–250
Schricker K, Potzl B, Hamann M, Kurtz A (1996) Coordinate changes of renin and brain-type nitric-oxide-synthase (b- NOS) mRNA levels in rat kidneys. Pflugers Arch 432:394–400
Singh I, Grams M, Wang WH, Yang T, Killen P, Smart A, Schnermann J, Briggs JP (1996) Coordinate regulation of renal expression of nitric oxide synthase, renin, and angiotensinogen mRNA by dietary salt. Am J Physiol 270:F1027–F1037
Christopherson KS, Hillier BJ, Lim WA, Bredt DS (1999) PSD-95 assembles a ternary complex with the N-methyl-D-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J Biol Chem 274:27467–27473
Herrera M, Garvin JL (2005) Recent advances in the regulation of nitric oxide in the kidney. Hypertension 45:1062–1067
Grants
This work was supported by NIH grant 2R01HL52765–04A2 awarded to Michael J. Solhaug.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ratliff, B., Rodebaugh, J., Sekulic, M. et al. Nitric oxide synthase and renin–angiotensin gene expression and NOS function in the postnatal renal resistance vasculature. Pediatr Nephrol 24, 355–365 (2009). https://doi.org/10.1007/s00467-008-0977-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-008-0977-9