This Article Full Text Full Text (PDF) 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 Krenek, P. Articles by Godfraind, T. Search for Related Content PubMed PubMed Citation Articles by Krenek, P. Articles by Godfraind, T. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Blood Pressure Medicines Dietary Sodium High Blood Pressure Related Collections Remodeling Cardiovascular Pharmacology Cerebrovascular disease/stroke Other hypertension Hypertrophy Neuroprotectors

(Hypertension. 2001;37:1124.)
© 2001 American Heart Association, Inc.

Scientific Contributions

Lacidipine Prevents Endothelial Dysfunction in Salt-Loaded Stroke-Prone Hypertensive Rats

Peter Krenek; Salvatore Salomone; Jan Kyselovic; Maurice Wibo; Nicole Morel; Théophile Godfraind

From the Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium (P.K., S.S., M.W., N.M., T.G.); and the Department of Pharmacology and Toxicology, Pharmaceutical Faculty of the Comenius University, Bratislava, Slovak Republic (J.K.).

Correspondence to Prof Théophile Godfraind, Université Catholique de Louvain, Laboratoire de Pharmacologie, UCL 54.10, Avenue Hippocrate 54, B-1200 Brussels, Belgium. E-mail godfraind{at}farl.ucl.ac.be

Abstract—Endothelium-dependent vasorelaxation is defective in hypertensive rats, especially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute to the pathogenesis of stroke independent of blood pressure. Because treatment with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the effect of this treatment on endothelium-dependent vasorelaxation in the aorta. Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking water) with or without lacidipine (1 mg · kg^-1 · d^-1) for 6 weeks. A high-sodium diet (1) increased systolic blood pressure, aortic weight, and wall thickness and plasma renin activity (P<0.05); (2) markedly reduced nitric oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-acetylpenicillamine, an NO donor (P<0.001); and (3) induced an elevation of preproendothelin-1 mRNA levels in aortic tissue (P<0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the salt-dependent functional and structural alterations of the aorta, including the overexpression of the preproendothelin-1 gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P<0.01). In conclusion, lacidipine protects stroke-prone hypertensive rats against the impairment of endothelium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and stroke.

Key Words: calcium channel blockers • calcium antagonists • hypertension, sodium-dependent • endothelium • endothelin • nitric oxide

This article has been cited by other articles:

				T. Godfraind Antioxidant effects and the therapeutic mode of action of calcium channel blockers in hypertension and atherosclerosis Phil Trans R Soc B, December 29, 2005; 360(1464): 2259 - 2272. [Abstract] [Full Text] [PDF]

				J. Zhu, T. Mori, T. Huang, and J. H. Lombard Effect of high-salt diet on NO release and superoxide production in rat aorta Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H575 - H583. [Abstract] [Full Text] [PDF]

				S. Kagota, A. Tamashiro, Y. Yamaguchi, K. Nakamura, and M. Kunitomo High Salt Intake Impairs Vascular Nitric Oxide/Cyclic Guanosine Monophosphate System in Spontaneously Hypertensive Rats J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 344 - 351. [Abstract] [Full Text] [PDF]

				X. Chen, R. M. Touyz, J. B. Park, and E. L. Schiffrin Antioxidant Effects of Vitamins C and E Are Associated With Altered Activation of Vascular NADPH Oxidase and Superoxide Dismutase in Stroke-Prone SHR Hypertension, September 1, 2001; 38(3): 606 - 611. [Abstract] [Full Text] [PDF]