Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats

Endothelium-dependent vasorelaxation is defective in hypertensive rats, esp ecially in conduit arteries. In the stroke-prone spontaneously hypertensive rat, impaired endothelium-dependent vasorelaxation appears to contribute t o the pathogenesis of stroke independent of blood pressure. Because treatme nt with lacidipine, a long-acting calcium channel blocker, protects against stroke and cardiovascular remodeling in this model, we investigated the ef fect of this treatment on endothelium-dependent vasorelaxation in the aorta . Stroke-prone rats were exposed to a salt-rich diet (1% NaCl in drinking w ater) with or without lacidipine (1 mg . kg(-1) . d(-1)) for 6 weeks. A hig h-sodium diet (1) increased systolic blood pressure, aortic weight, and wal l thickness and plasma renin activity (P <0.05); (2) markedly reduced nitri c oxide (NO)-mediated, endothelium-dependent relaxation of aortic rings to acetylcholine and the sensitivity to the relaxing effect of S-nitroso-N-ace tylpenicillamine, an NO donor (P <0.001); and (3) induced an elevation of p reproendothelin-l mRNA levels in aortic tissue (P <0.01) without affecting endothelial NO synthase mRNA levels. Lacidipine treatment prevented the sal t-dependent functional and structural alterations of the aorta, including t he overexpression of the preproendothelin-l gene, and increased endothelial NO synthase mRNA levels in aortic tissue (P <0.01). In conclusion, lacidip ine protects stroke-prone hypertensive rats against the impairment of endot helium-dependent vasorelaxation evoked by a salt-rich diet, and this effect may contribute to its beneficial effect against end-organ damage and strok e.