Lacidipine prevents endothelial dysfunction in salt-loaded stroke-prone hypertensive rats.
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.
Krenek
P
P
Laboratoire de Pharmacologie, Université Catholique de Louvain, Brussels, Belgium.
Salomone
S
S
Kyselovic
J
J
Wibo
M
M
Morel
N
N
Godfraind
T
T
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D019332:Endothelin-1 / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects*; D015870:Gene Expression; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012982:Sodium, Dietary / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D019332:Endothelin-1; D012982:Sodium, Dietary; C060285:lacidipine; D019001:Nitric Oxide Synthase