Atheroprotective effects of long-acting dihydropyridine-type calcium channel blockers: evidence from clinical trials and basic scientific research.
Atherosclerosis is a systemic disease that can ultimately lead to ischaemia and infarction in the heart, brain and peripheral vasculature. According to the "response to injury" hypothesis, endothelial dysfunction is the early event that allows penetration of lipids and inflammatory cells into the arterial wall, contributing to the development of the atherosclerotic lesion. Endothelial dysfunction is causally related to a variety of risk factors for atherosclerosis, including hyperlipidaemia and hypertension. Agents that restore endothelial function and NO bioavailability have beneficial anti-atherogenic activities and can improve cardiovascular outcomes; this has been observed with angiotensin-converting enzyme (ACE) inhibitors, statins and certain dihydropyridine-type calcium channel blockers (CCBs). In the Prospective Randomised Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), the CCB amlodipine provided significant clinical benefits compared with placebo, including a marked reduction in cardiovascular morbidity and a reduction in the progression of carotid atherosclerosis. As these beneficial effects of amlodipine have not been observed with other dihydropyridine-type CCBs, it has been proposed that this agent has distinct anti-atherosclerotic properties related to its strong lipophilicity and membrane location. Experimental support for this hypothesis has been obtained from various in vitro and in vivo models of atherosclerosis. These findings support a broader therapeutic role for third-generation dihydropyridine-type CCBs in the treatment of atherosclerosis.
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. rpmason@elucidaresearch.com
R Preston
RP
Mason
D001161:Arteriosclerosis / Q000517:prevention & control*; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000627:therapeutic use*; D003692:Delayed-Action Preparations / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000008:administration & dosage* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008955:Models, Cardiovascular; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D004095:Dihydropyridines; C038806:1,4-dihydropyridine