PT - JOURNAL ARTICLE AU - Jan Kyselovic AU - Peter Martinka AU - Zuzana Batova AU - Andrea Gazova AU - Theophile Godfraind TI - Calcium Channel Blocker Inhibits Western-Type Diet-Evoked Atherosclerosis Development in ApoE-Deficient Mice AID - 10.1124/jpet.105.089847 DP - 2005 Oct 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 320--328 VI - 315 IP - 1 4099 - http://jpet.aspetjournals.org/content/315/1/320.short 4100 - http://jpet.aspetjournals.org/content/315/1/320.full SO - J Pharmacol Exp Ther2005 Oct 01; 315 AB - Calcium channel blockers slow the progression of atherosclerosis. The purpose of the present experiments was to examine the action of lacidipine in a condition that accelerates the development of atherosclerosis in order to test the hypothesis that the protective action of lacidipine in atherosclerosis is unrelated to the reduction of blood pressure. Male ApoE-deficient mice (6 weeks old) were exposed either to normal chow (ND) or to a Western-type diet (WD, adjusted calorie diet containing 42% from fat) for 8 weeks. Western-type diet induced a reduction of nitric oxide (NO)-mediated endothelium-dependent relaxation to acetylcholine (Max relaxation % = 55.8 ± 2 for ND and 46.6 ± 2 for WD, n = 8, p < 0.05). Dose-relaxation curves to S-nitroso-N-acetylpenicillamine (SNAP) NO donor were also significantly rightward-shifted (n = 7, ANOVA, p < 0.01) in WD compared with ND arteries. Chronic treatment of WD mice with lacidipine (1 and 3 mg/kg/day) increased significantly the acetylcholine-evoked relaxation (to 76.6 ± 3.5%, n = 6, ANOVA, p < 0.001) and prevented the loss of responsiveness to SNAP in mice exposed to WD. Plasma renin activity and endothelin-1 plasma levels as well as thiobarbituric acid-reactive substance levels in kidneys were significantly lower in WD mice treated with lacidipine than in untreated ones. In mice exposed to WD lacidipine reduced extension of atherosclerotic lesions, renal injury and increase in blood pressure. Experimental data indicate that inhibition of Western-type diet-evoked alterations is related to both antioxidant and vasoactive properties of lacidipine. The American Society for Pharmacology and Experimental Therapeutics