Abstract
Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II(AII)-induced vasoconstrictions. Kidenys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10-5 M indomethacin. RVR decreased with age from 12.7 ± 0.6 at 1 wk to 10.1 ± 0.5 mm Hg min g mL-1 at 6 wk. Nω-Nitro-L-arginine methyl ester (L-NAME, 10-4 M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10-8 M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10-10 M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postanatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- AII:
-
angiotensin II
- IPK:
-
isolated perfused kidney
- L-NAME:
-
Nω-nitro-L-arginine methyl ester
- NO:
-
nitric oxide
- NOS:
-
nitric oxide synthase
- RVR:
-
renal vascular resistance
- RBF:
-
renal blood flow
- AT1, AT2:
-
angiotensin receptor subtypes 1, 2
References
Gruskin AB, Edelmann CM Jr, Yan S 1970 Maturational changes in renal blood flow in piglets. Pediatr Res 4: 7–13.
Guignard JP, Torrado A, Da Cunha O, Gautier E 1975 Glomerular filtration rate in the first three weeks of life. J Pediatr 87: 268–272.
Arant BS Jr 1978 Developmental patterns of renal function maturation compared in the human neonate. J Pediatr 92: 705–712.
Bueva A, Guignard JP 1994 Renal function in preterm neonates. Pediatr Res 36: 572–577.
Tufro-McReddie A, Gomez RA 1993 Ontogeny of the renin-angiotensin system. Semin Nephrol 13: 519–530.
Solhaug MJ, Wallace MR, Granger JP 1993 Endothelium-derived nitric oxide modulates renal hemodynamics in the developing piglet. Pediatr Res 34: 750–754.
Bogaert GA, Kogan BA, Mevorach RA 1993 Effects of endothelium-derived nitric oxide on renal hemodynamics and function in the sheep fetus. Pediatr Res 34: 755–761.
Cocks TM, Angus JA 1983 Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature 305: 627–630.
Conrad KP, Whittemore SL 1992 NG-Monomethy1-L-arginine and nitroarginine potentiate pressor responsiveness of vasoconstrictors in conscious rats. Am J Physiol 262:R1137–R1144.
Ito S, Juncos LA, Nushiro N, Jonhson CS, Carretero OA 1991 Endothelium-derived relaxing factor modulates endothelin action in afferent arterioles. Hypertension 17: 1052–1056.
Ito S, Johnson CS, Carretero OA 1991 Modulation of angiotensin II-induced vasoconstriction by endothelium-derived relaxing factor in the isolated microperfused rabbit afferent arteriole. J Clin Invest 87: 1656–1663.
Baylis C, Harvey J, Engels K 1994 Acute nitric oxide blockade amplifies the renal vasoconstrictor actions of angiotensin II. J Am Soc Nephrol 5: 211–214.
Alberola AM, Salazar FJ, Nakamura T, Granger JP 1994 Interaction between angiotensin II and nitric oxide in control of renal hemodynamics in conscious dogs. Am J Physiol 267:R1472–R1478.
Ito S, Arima S, Ren YL, Juncos LA, Carretero OA 1993 Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. J Clin Invest 91: 2012–2019.
Ohishi K, Carmines PK, Inscho EW, Navar LG 1992 EDRF-angiotensin II interactions in rat juxtamedullary afferent and efferent arterioles. Am J Physiol 263:F900–F906.
Sigmon DH, Carretero OA, Beierwaltes WH 1992 Angiotensin dependence of endothelium-mediated renal hemodynamics. Hypertension 20: 643–650.
Sigmon DH, Carretero OA, Beierwaltes WH 1992 Plasma renin activity and the renal response to nitric oxide synthesis inhibition. J Am Soc Nephrol 3: 1288–1294.
Hajj-ali AF, Zimmerman BG 1992 Nitric oxide participation in renal hemodynamic effect of angiotensin converting enzyme inhibitor lisinopril. Eur J Pharmacol 212: 279–281.
Sigmon DH, Beierwaltes WH 1993 Renal nitric oxide and angiotensin II interaction in renovascular hypertension. Hypertension 22: 237–242.
Robillard JE, Weismann DN, Gomez A, Ayres NA, Lawton WJ, Van Orden DE 1983 Renal and adrenal responses to converting-enzyme inhibition in fetal and newborn life. Am J Physiol 244:R249–R256.
Osborn JL, Hook JB, Bailie MD 1980 Effects of saralasin and indomethacin on renal function in developing piglets. Am J Physiol 238:R438–R442.
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.
Kazimierczak J 1963 Histochemical study of oxidative enzymes in rabbit kidney before and after birth. Acta Anat 55: 352–369.
Godard C, Gaillard R, Vallotton MB 1976 The renin-angiotensin-aldosterone system in mother and fetus at term. Nephron 17: 353–360.
Robillard JE, Nakamura KT, Matherne GP, Jose PA 1988 Renal hemodynamics and functional adjustments to postnatal life. Semin Perinatol 12: 143–150.
Gomez RA, Robillard JE 1984 Developmental aspects of the renal responses to angiotensin II in fetal lambs and adult sheep. Circ Res 54: 301–312.
Pupilli C, Gomez RA, Tuttle JB 1991 Spatial association of renin-containing cells and nerve fibers in developing rat kidney. Pediatr Nephrol 5: 690–695.
Robillard JE, Nakamura KT 1988 Neurohormonal regulation of renal function during development. Am J Physiol 254:F850–F858.
Gleason CA 1987 Prostaglandins and the developing kidney. Semin Perinatol 11: 12
Robillard JE, Gomez RA, Van Orden DE 1982 Comparison of the adrenal and renal responses to angiotensin II in fetal lambs and adult sheep. Circ Res 50: 140–147.
Aguilera G, Kapur S, Feuillan P, Sunar-Akbasak B, Bathia AJ 1994 Developmental changes in angiotensin II receptor subtypes and AT1 receptor mRNA in rat kidney. Kidney Int 46: 973–979.
Baylis C, Engels K, Samsell L, Harton P 1993 Renal effects of acute endothelium-derived relaxing factor blockade are not mediated by angiotensin II. Am J Physiol 264: F74–F78.
Pucci ML, Lin L, Nasjletti A 1992 Pressor and renal vasoconstrictor effects of NG-nitro-L-arginine as affected by blockade of pressor mechanisms mediated by the sympathetic nervous system, angiotensin, prostanoids and vasopressin. J Pharmacol Exp Ther 261: 240–245.
Sigmon DH, Newman JM, Beierwaltes WH 1994 Angiotensin II-endothelium-derived nitric oxide interaction in conscious rats. J Am Soc Nephrol 4: 1675–1682.
Sigmon DH, Beierwaltes WH 1993 Angiotensin II-nitric oxide interaction and the distribution of blood flow. Am J Physiol 265:R1276–R1283.
Deng X, Welch WJ, Wilcox CS 1994 Renal vasoconstriction during inhibition of NO-synthase: effects of dietary salt. Kidney Int 46: 639–646.
Takenaka T, Mitchell KD, Navar LG 1993 Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat. J Am Soc Nephrol 4: 1046–1053.
Sigmon DH, Carretero OA, Beierwaltes WH 1992 Endothelium-derived relaxing factor regulates renin release in vivo. Am J Physiol 256:F256–F261.
Imig JD, Roman RJ 1992 Nitric oxide modulates vascular tone in preglomerular arterioles. Hypertension 19: 770–774.
Tamaki T, Hasui K, Aki Y, Kimura S, Abe Y 1993 Effects of N(G)-nitro-L-Arginine on isolated rabbit afferent arterioles. Jpn J Pharmacol 62: 231–237.
Busse R, Mulsch A, Fleming I, Hecker M 1993 Mechanisms of nitric oxide release from the vascular endothelium. Circulation 87: 18–25.
Parekh N, Dobrowolski L, Zou A-P, Steinhausen M 1996 Nitric oxide modulates angiotensin II- and norepinephrine-dependent vasoconstriction in rat kidney. Am J Physiol 270: R630–R635.
Acknowledgements
The authors thank Drs. N. Parekh and K.-H. Endlich for kindly reviewing the manuscript.
Author information
Authors and Affiliations
Additional information
Supported by the French National Institute of Health and Medical Research(INSERM), grant CJF 9409, the French Ministry of Higher Education (MENESR), EA 1314 and the French Medical Foundation.
Rights and permissions
About this article
Cite this article
Simeoni, U., Zhu, B., Muller, C. et al. Postnatal Development of Vascular Resistance of the Rabbit Isolated Perfused Kidney: Modulation by Nitric Oxide and Angiotensin II. Pediatr Res 42, 550–555 (1997). https://doi.org/10.1203/00006450-199710000-00022
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199710000-00022
This article is cited by
-
Neuronal nitric oxide synthase, nNOS, regulates renal hemodynamics in the postnatal developing piglet
Pediatric Research (2012)
