Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Jul;90(1):278–281. doi: 10.1172/JCI115849

Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage.

C Baylis 1, B Mitruka 1, A Deng 1
PMCID: PMC443093  PMID: 1634615

Abstract

Tonic basal release of nitric oxide (NO) by vascular endothelial cells controls blood pressure (BP) in the basal state. In these studies we investigated the effects of chronic inhibition of basal NO synthesis in the rat for a 2-mo period. Significant systemic hypertension developed in chronically NO-blocked rats compared to controls. Marked renal vasoconstriction was also observed with elevations in glomerular blood pressure (PGC) and reductions in the glomerular capillary ultrafiltration coefficient (Kf). Chronically NO-blocked rats also develop proteinuria and glomerular sclerotic injury compared to controls. These studies therefore describe a new model of systemic hypertension with glomerular capillary hypertension and renal disease due to chronic blockade of endogenous NO synthesis. These observations highlight the importance of the endogenous NO system in control of normal vascular tone and suggest that hypertensive states may result from relative NO deficiency.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aisaka K., Gross S. S., Griffith O. W., Levi R. NG-methylarginine, an inhibitor of endothelium-derived nitric oxide synthesis, is a potent pressor agent in the guinea pig: does nitric oxide regulate blood pressure in vivo? Biochem Biophys Res Commun. 1989 Apr 28;160(2):881–886. doi: 10.1016/0006-291x(89)92517-5. [DOI] [PubMed] [Google Scholar]
  2. Baylis C., Deen W. M., Myers B. D., Brenner B. M. Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex. Am J Physiol. 1976 Apr;230(4):1148–1158. doi: 10.1152/ajplegacy.1976.230.4.1148. [DOI] [PubMed] [Google Scholar]
  3. Baylis C., Harton P., Engels K. Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney. J Am Soc Nephrol. 1990 Dec;1(6):875–881. doi: 10.1681/ASN.V16875. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Brenner B. M. Nephron adaptation to renal injury or ablation. Am J Physiol. 1985 Sep;249(3 Pt 2):F324–F337. doi: 10.1152/ajprenal.1985.249.3.F324. [DOI] [PubMed] [Google Scholar]
  6. Chen P. Y., Sanders P. W. L-arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest. 1991 Nov;88(5):1559–1567. doi: 10.1172/JCI115467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Regional haemodynamic changes during oral ingestion of NG-monomethyl-L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol. 1990 Sep;101(1):10–12. doi: 10.1111/j.1476-5381.1990.tb12079.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Garg U. C., Hassid A. Inhibition of rat mesangial cell mitogenesis by nitric oxide-generating vasodilators. Am J Physiol. 1989 Jul;257(1 Pt 2):F60–F66. doi: 10.1152/ajprenal.1989.257.1.F60. [DOI] [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Mauer S. M., Steffes M. W., Ellis E. N., Sutherland D. E., Brown D. M., Goetz F. C. Structural-functional relationships in diabetic nephropathy. J Clin Invest. 1984 Oct;74(4):1143–1155. doi: 10.1172/JCI111523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  13. Raij L., Azar S., Keane W. Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int. 1984 Aug;26(2):137–143. doi: 10.1038/ki.1984.147. [DOI] [PubMed] [Google Scholar]
  14. Rees D. D., Palmer R. M., Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989 May;86(9):3375–3378. doi: 10.1073/pnas.86.9.3375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zatz R., de Nucci G. Effects of acute nitric oxide inhibition on rat glomerular microcirculation. Am J Physiol. 1991 Aug;261(2 Pt 2):F360–F363. doi: 10.1152/ajprenal.1991.261.2.F360. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES