This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Schnermann, J. Articles by Briggs, J. P Search for Related Content PubMed Articles by Schnermann, J. Articles by Briggs, J. P Social Bookmarking                         What's this?

Angiotensin II blockade causes acute renal failure in eNOS-deficient mice

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA, jurgens@ intra.niddk.nih.gov

Yuning G Huang

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA

Josie P Briggs

National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA

Compared with wild-type mice, adult endothelial nitric oxide synthase (eNOS) knockout mice (eight months of age) have increased blood pressure (BP) (126±9 mmHg vs. 100±4 mmHg), and an increased renal vascular resistance (155±16 vs. 65±4 mmHg.min/ml). Renal vascular resistance responses to i.v. administration of noradrenaline were markedly enhanced in eNOS knockout mice. Glomerular filtration rate (GFR) of anaesthetised eNOS -/- mice was 324±57 µl/min gKW, significantly lower than the GFR of 761±126 µl/min.gKW in wild-type mice. AT₁-receptor blockade with i.v. candesartan (1—1.5 mg/kg) reduced arterial blood pressure and renal vascular resistance, and increased renal blood flow (RBF) to about the same extent in wild-type and eNOS -/- mice. Candesartan did not alter GFR in wild-type mice (761±126 vs. 720±95 µl/min.gKW), but caused a marked decrease in GFR in eNOS -/- mice (324.5±75.2 vs. 77±18 µl/min.gKW). A similar reduction in GFR of eNOS deficient mice was also caused by angiotensin-converting enzyme (ACE) inhibition. Afferent arteriolar granularity, a measure of renal renin expression, was found to be reduced in eNOS -/- compared with wild-type mice. In chronically eNOS-deficient mice, angiotensin II (Ang II) is critical for maintaining glomerular filtration pressure and GFR, presumably through its effect on efferent arteriolar tone.

Key Words: candesartan • quinapril • nitric oxide synthase • glomerular filtration rate • renal blood flow • endothelium

References

• Baylis C., Harton P., Engels K. Endothelial derived relaxing factor controls renal hemodynamics in the normal rat kidney. J Am Soc Nephrol 1990;1:875-81.[Abstract]
• Baylis C., Mitruka B., Deng A. Chronic blockade of nitric oxide synthesis in the rat produces systemic hypertension and glomerular damage. J Clin Invest 1992;90:278-81.[Web of Science][Medline] [Order article via Infotrieve]
• Qiu C., Baylis C. Endothelin and angiotensin mediate most glomerular responses to nitric oxide inhibition. Kidney Int 1999;55:2390-96.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Takenaka T., Mitchell KD, Navar LG Contribution of angiotensin II to renal hemodynamic and excretory responses to nitric oxide synthesis inhibition in the rat. J Am Soc Nephrol 1993;4:1046-53.[Abstract]
• Shesely EG, Maeda N., Kim H-S. et al. Elevated blood pressure in mice lacking endothelial nitric oxide synthase. Proc Nat Acad Sci USA 1996;93:13176-81.[Abstract/Free Full Text]
• Beck E., Ludwig G., Auerswald EA, Reiss B., Schaller H. Nucleotide sequence and exact localization of the neomycin phosphotransferase gene from transposon Tn5. Gene 1982;19: 327-36.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Casellas D., Dupont M., Kaskel FJ, Inagami T., Moore LC Direct visualization of renin-cell distribution in preglomerular vascular trees dissected from rat kidney. Am J Physiol Renal Physiol 1993;265(1 Pt 2):F151-6.[Abstract/Free Full Text]
• Huang PL, Huang Z., Mashimo H. et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995;377:239-42.[CrossRef][Medline] [Order article via Infotrieve]
• Kojda G., Laursen JB, Ramasamy S. et al. Protein expression, vascular reactivity and soluble guanylate cyclase activity in mice lacking the endothelial nitric oxide synthase: contributions of NOS isoforms to blood pressure and heart rate control. Cardiovasc Res 1999;42:206-13.[Abstract/Free Full Text]
• Maeso R., Navarro-Cid J.,Rodrigo E., Ruilope LM, Cachofeiro V., Lahera V. Effects of antihypertensive therapy on factors mediating endothelium-dependent relaxation in rats treated chronically with L-NAME. J Hypertens 1999;17:221-7.[Web of Science][Medline] [Order article via Infotrieve]
• Sigmon DH, Carretero OA, Beierwaltes WH Plasma renin activity and the renal response to nitric oxide synthesis inhibition. J Am Soc Nephrol 1992;3:1288-94.[Abstract]
• Turkstra E., Braam B., Koomans HA Losartan attenuates modest but not strong renal vasoconstriction induced by nitric oxide inhibition. J Cardiovasc Pharm 1998;32:593-600.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Baylis C., Engels K., Samsell L., Harton P. Renal effects of acute endothelial-derived relaxing factor blockade are not mediated by angiotensin II. Am J Physiol Renal Physiol 1993;264:F74-F8.[Abstract/Free Full Text]
• Deng X., Welch WJ, Wilcox CS Renal vasoconstriction during inhibition of NO synthase: effect of dietary salt. Kidney Int 1994;46:639-46.[Web of Science][Medline] [Order article via Infotrieve]
• Esmail ZN, Loewen PS Losartan as an alternative to ACE inhibitors in patients with renal dysfunction. Ann Pharmacother 1998;32:1096-8.[Abstract]
• Levenson DJ, Dzau VJ Effects on angiotensin-converting enzyme inhibition on renal hemodynamics in renal artery stenosis. Kidney Int 1987;31 (Suppl 20):S-173-S-179.[Web of Science]
• Toto RD Renal insufficiency due to angiotensin-converting enzyme inhibitors. Miner Electrolyte Metab 1994;20:193-200.[Web of Science][Medline] [Order article via Infotrieve]
• Majid DSA, Williams A., Navar LG Inhibition of nitric oxide synthesis attenuates pressure-induced natriuretic responses in anesthetized dogs. Am J Physiol Renal Physiol 1993;264:F79-F87.[Abstract/Free Full Text]
• Wagner C., Godecke A., Ford M., Schnermann J., Schrader J., Kurtz A. Regulation of renin gene expression in kidneys of eNOS- and nNOS-deficient mice. Pflugers Arch 2000; 439(5):567-72.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S199-S203 (2001)
DOI: 10.1177/14703203010020013501


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. B. Hansen, S. Hashimoto, M. Oppermann, Y. Huang, J. P. Briggs, and J. Schnermann Vasoconstrictor and Vasodilator Effects of Adenosine in the Mouse Kidney due to Preferential Activation of A1 or A2 Adenosine Receptors J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1150 - 1157. [Abstract] [Full Text] [PDF]

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Schnermann, J. Articles by Briggs, J. P Search for Related Content PubMed Articles by Schnermann, J. Articles by Briggs, J. P Social Bookmarking                         What's this?