Calcium Channel Blocker Inhibits Western-Type Diet-Evoked Atherosclerosis Development in ApoE-Deficient Mice

Abstract

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 % ϭ 55.8 Ϯ 2 for ND and 46.6 Ϯ 2 for WD, n ϭ 8, p Ͻ 0.05). Dose-relaxation curves to S-nitroso-N-acetylpenicillamine (SNAP) NO donor were also significantly rightward-shifted (n ϭ 7, ANOVA, p Ͻ 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 Ϯ 3.5%, n ϭ 6, ANOVA, p Ͻ 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 acidreactive 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.

Regression of Atherosclerosis by Amlodipine via Anti-Inflammatory and Anti-Oxidative Stress Actions

“…These inhibitory actions of amlodipine were accompanied by inhibitions of oxidative stress and the inflammatory response. It appears that this type of inhibitory action on atherosclerosis is not specific to amlodipine, since similar effects have been observed in experimental studies with the CCBs azelnidipine (11) and lacinidipine (17,18), as well as in a clinical study with these agents (19).…”

Cadmium and cardiovascular diseases: cell biology, pathophysiology, and epidemiological relevance

“…Importantly, it has to be mentioned that the situation (bound to free ion) in the circulation (the blood stream) need not necessarily reflect the situation in the microenvironment on the surface of endothelial cells. Other uptake routes for the free ion include ZIP8 (mainly responsible in testicular endothelial cell uptake of Cd), calcium-channels (Kyselovic et al 2005), plasma membrane-associated DMT-1 (Simovich et al 2002), and other ion pumps and transporters; the physiological relevance of these Cd uptake pathways in endothelial cell subtypes remains to be investigated (Prozialeck et al 2008).…”

Self-eating in the plaque: what macrophage autophagy reveals about atherosclerosis

“…These include agents that target upstream regulators of autophagy such as mTOR [83–85], inositol/IP 3 [86, 87], calcium [88–90], and dopamine [91]. Although all pharmacologic strategies are plagued with non-specificity, the most straightforward approach is direct targeting of mTOR signaling (Box 1, Figure I) [92, 93].…”