Background: Reduction in renal mass is associated with several structural and functional adaptations including compensatory renal growth and hemodynamic changes. The mediators of the renal hemodynamic adaptations have not been definitively identified. Several investigators have postulated that nitric oxide (NO) is involved this physiological mechanisms. The purpose of this study was to evaluate the role of vascular and renal NO pathway in the model of subtotal nephrectomy-salt load hypertension. Materials and Methods: Wistar rats with 75% renal mass reduction (RMR) and saline load were studied during 4 weeks. Weekly, indirect systolic blood pressure (SBP) were measured. One week after nephrectomy, animals were divided in two groups, hypertensive (SBP > 140 mm Hg) and normotensive (SBP < 140 mm Hg). Urinary excretion of nitrates and nitrites (NOx), urinary chemioluminiscence levels and NOS activity in the left kidney and in the thoracic aorta artery were determined at the fourth week after subtotal nephrectomy. Results: Urinary excretion of sodium was higher in normotensive rats than hypertensive rats and in both groups this parameter was higher than in sham rats. NOx excretion and NOS activity in the different nephron segments were higher in normotensive rats than in the hypertensive ones. In contrast, NOS activity in aorta sections and urinary chemiluminescence levels in hypertensive animals were enhanced compared with normotensive rats. These parameters were higher in both groups of nephrectomized rats than in sham ones. Conclusion: This study provides evidence to support the fact that the activation of the renal NO system is an important mechanism whereby the remnant kidney regulates sodium and water balance, contributing to control the arterial blood pressure in the renal mass reduction and saline load model.

1.
Anderson S, Meyer TW, Brenner BM: The role of hemodynamic factors in the initiation and progression of renal disease. J Urol 1985;133:310–315.
2.
Martínez Seeber A, Balaszczuk AM, Villamil MF: Glomerulotubular balance in hypertensive rats. Nephron 1981;27:89–93.
3.
Yoshida Y, Fogo A, Ichikawa I: Glomerular hemodynamic changes vs. hypertrophy in experimental glomerular sclerosis. Kidney Int 1989;35:654–660.
4.
Pamnani MB, Bryant HJ, Haddy FJ: Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension. Hypertension 1987;10:178–183.
5.
Costa ML, Loria A, Marchetti M, Balaszczuk AM, Arranz C: Effects of dopamine and nitric oxide on arterial pressure and renal function in volume expansion. Clin Exp Pharmacol Physiol 2002;29:772–776.
6.
Lahera V, Salom MG, Miranda-Guardiola F, Moncada S, Romero JC: Effects of N-nitro-L-arginine methylester on renal function and blood pressure. Am J Physiol 1991;261:F1033–F1037.
7.
Wennmalm A, Benthin G, Edlund A, Jungersten L, Kieler-Jensen N, Lundin S, Nathorst-Westfelt U, Petersson AS, Waagstein F: Metabolism and excretion of nitric oxide in humans: An experimental and clinical study. Circ Res 1993;73:1121–1127.
8.
Kone BC, Baylis C: Biosynthesis and homeostatic roles of nitric oxide in the normal kidney. Am J Physiol 1997;272:F561–F578.
9.
Manning RD, Hu L: Nitric oxide regulates renal haemodynamics and urinary sodium excretion in dogs. Hypertension 1994;23:619–625.
10.
Zatz R, De Nucci G: Effects of acute nitric oxide inhibition on rat glomerular microcirculation. Am J Physiol 1991;261:F360–F363.
11.
Zou AP, Cowley AW: Role of nitric oxide in the control of renal function and salt sensitivity. Curr Hypertens Rep 1999;1:178–186.
12.
Chen C, Mitchell KD, Navar LG: Role of endothelium derived nitric oxide in the renal hemodynamic response to amino acid infusion. Am J Physiol 1992;263:R510–R516.
13.
Reyes AA, Purkerson ML, Karl I, Klahr S: Dietary supplementation of L-arginine ameliorates the progression of renal disease in rats with subtotal nephrectomy. Am J Kidney Dis 1992;20:168–176.
14.
Ashab I, Peer G, Blum M, Wollman Y, Chernihovsky T, Hassner A, Schwartz D, Cabili S, Silverberg D, Iaina A: Oral administration of L- arginine and captopril in rats prevents chronic renal failure by nitric oxide production. Kidney Int 1995;47:1515–1521.
15.
Dauda G, Kazda S, Orth H, Gross F: Reduction of renal mass and hypertension; in Genest J, Koiw E (eds): Hypertension 72. Berlin, Springer, 1972, pp 127–139.
16.
Verdon CP, Burton BA, Prior RL: Sample pretreatment with nitrate reductase and glucose–6-Phosphate dehydrogenase quantitatively reduces nitrate while avoiding interference by NADP+ when the Griess reaction is used to assay for nitrite. Analy Biochem 1995;224:502–508.
17.
Lissi EA, Salim-Hanna M, Videla LA: Spontaneous urinary visible luminescence: Characteristics and modification by oxidative stress-related clinical conditions. Braz J Med Biol Res 1994;27:1491–1505.
18.
Vincent S, Kimura H: Histochemical mapping of nitric oxide synthase in the rat brain. Neuroscience 1992;46:755–784.
19.
Stuehr DJ, Cho HJ, Kwon NS, Weise M, Nathan CF: Purification and characterization of the cytokine-induced macrophage nitric oxide synthase: A FAD- and FMN-containin flavoprotein. Proc Natl Acad Sci USA 1991;88:7773–7777.
20.
Rothe F, Canzler U, Wolf G: Subcellular localization of the neuronal isoform of nitric oxide synthase in the rat brain: A critical evaluation. Neurosci 1998;83:259–269.
21.
Arranz CT, Laclaustra AM, Domínguez AE, Vidal NA, Fernández BE, Martínez Seeber A: Characteristics of the arterial hypertension of subtotal nephrectomy in the rat. Rev Esp Fisiol 1981;37:437–442.
22.
Pamnani MB, Mueller GP, Ghird RD, Hady FJ: Role of atrial natriuretic factor in regulation of blood pressure in normotensive rats having reduced renal mass. Proc Soc Exp Biol Med 1988;189:297–303.
23.
Besim Ö, Ayse D: Interaction between AVP and sympathetic system in subtotal nephrectomy-saline hypertension: role of α and V1 receptors. J Autonom Nerv Syst 2000;78:165–171.
24.
Hout SJ, Motilal, B, Pamnani, MB, Clough, DL, Buggy J, Bryant HJ, Harder DL, Haddy FJ: Sodium-potassium pump activity in reduced renal-mass hypertension. Hypertension 1983;5(suppl I):I94–I100.
25.
Mattson DL, Wu F: Control of arterial blood pressure and renal sodium excretion by nitric oxide synthase in the renal medulla. Acta Physiol Scand 2000;168:149–154.
26.
Costa MA, Marchetti M, Balaszczuk AM, Arranz CT: Effects of L-arginine and furosemide on blood pressure and renal function in volume expanded rats. Clin Exp Pharmacol Physiol 2001;28:528–532.
27.
Buga GM, Gold ME, Fukuto JM, Ignarro LJ: Shear stress induced release of nitric oxide from endothelial cells grown on beds. Hypertension 1991;17:187–193.
28.
Koller A, Kalley G: Endotelial regulation of wall shear stress and blood flow in skeletal muscle microcirculation. Am J Physiol 1991;260:H862–H868.
29.
Tojo A, Madsen KM, Wilcox CS: Expression of immunoreactive nitric oxide synthase isoforms in rat kidney: Effects of dietary salt and losartan. Jpn Heart J 1995;36:389–398.
30.
Mattson DL, Higgins DJ: Influence of dietary sodium intake on renal medullary nitric synthase. Hypertension 1996;27:688–692.
31.
Lymar SV, Jiang Q, Hurst JKJ: Mechanism of carbon dioxide-catalyzed oxidation of tyrosine by peroxynitrite. Biochemistry 1996;35:7855–7861.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.