This Article Full Text Full Text (PDF) All Versions of this Article: 42/5/937    most recent 01.HYP.0000099240.89890.94v1 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 Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ying, L. Articles by Chansel, D. Search for Related Content PubMed PubMed Citation Articles by Ying, L. Articles by Chansel, D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CAPTOPRIL NITRIC OXIDE SODIUM CHLORIDE Related Collections Cardiovascular Pharmacology Animal models of human disease Other hypertension

(Hypertension. 2003;42:937.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Renal Effects of Omapatrilat and Captopril in Salt-Loaded, Nitric Oxide–Deficient Rats

Lu Ying; Martin Flamant; Sophie Vandermeersch; Jean-Jacques Boffa; Christos Chatziantoniou; Jean-Claude Dussaule; Dominique Chansel

From INSERM U489, Hôpital Tenon, and AP-HP (J.-C.D.), Department of Physiology, Hôpital St-Antoine, Paris, France.

Correspondence to Dominique Chansel, INSERM U489, Hôpital Tenon, 4, rue de la Chine, 75970 Paris cedex 20, France. E-mail dominique.chansel{at}tnn.ap-hop-paris.fr

Inhibition of nitric oxide synthases causes systemic hypertension and renal injury in rats. Our objective was to examine whether omapatrilat, a vasopeptidase inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase, could induce better regression of renal injury than ACE inhibitor alone. Ten groups of rats were studied. They were fed either a normal (0.8% NaCl) or a high (4% NaCl) sodium diet. Eight of these groups received N^G-nitro-L-arginine methyl ester (L-NAME, 20 mg · kg^-1 · d^-1) in their drinking water. After 4 weeks, 1 group on each diet was killed and considered the L-NAME group, whereas the others received L-NAME alone, captopril (200 mg · kg^-1 · d^-1) plus L-NAME, or omapatrilat (80 mg · kg^-1 · d^-1) plus L-NAME for 4 additional weeks. In rats receiving L-NAME alone for 8 weeks, the mortality rate was 90%, irrespective of the diet. In contrast, all rats survived in the captopril and the omapatrilat groups. In rats fed a normal-sodium diet, captopril and omapatrilat normalized systolic blood pressure and induced a complete regression of renal injury. Creatinine clearance and proteinuria were also normalized. In the high-sodium-diet groups, both treatments were less efficient: blood pressure remained elevated, and the regression of renal fibrosis was only partial. Although proteinuria decreased significantly with captopril or omapatrilat, creatinine clearance remained lower than in the controls. These results demonstrate that, in nitric oxide–deficient rats fed a normal-sodium diet, ACE and vasopeptidase inhibitors exhibit a marked renoprotective effect, whereas these treatments are less efficient in rats fed a high-sodium diet.

Key Words: hypertension, renal • kidney failure • angiotensin-converting enzyme • peptides • nitric oxide • sodium, dietary

This article has been cited by other articles:

				M. Flamant, S. Placier, A. Rodenas, C. A. Curat, W. F. Vogel, C. Chatziantoniou, and J.-C. Dussaule Discoidin Domain Receptor 1 Null Mice Are Protected against Hypertension-Induced Renal Disease J. Am. Soc. Nephrol., December 1, 2006; 17(12): 3374 - 3381. [Abstract] [Full Text] [PDF]

				M.-S. Zhou, E. A. Jaimes, and L. Raij Atorvastatin Prevents End-Organ Injury in Salt-Sensitive Hypertension: Role of eNOS and Oxidant Stress Hypertension, August 1, 2004; 44(2): 186 - 190. [Abstract] [Full Text] [PDF]