Antioxidant Dihydropyridines, A New And Comprehensive Therapy For Free Radical-Induced Cardiovascular Diseases

The generation of free radicals has been implicated in the pathologies of a number of cardiovascular diseases like infarction, stroke and atherosclerosis. Free radicals initiate lipid peroxidation, which leads to the impairment of membrane function and finally cell death. This often results in irrecoverable tissue damage. Therefore, potentially useful drugs would be those that not only have effects on the symptoms of the disease, but also demonstrate antioxidant and free radical scavenging properties. Some calcium entry blockers (CEBs) of the dihydropyridine (DHP) family (e.g. lacidipine, amlodipine, nifedipine) have been shown to possess radical scavenging activity in addition to their potent vasorelaxant properties. Some DHPs are active in inhibiting the autoperoxidation of rat cortical membranes. The order of potency was lacidipine>nimodipine>nifedipine, with lacidipine having an activity comparable to vitamin E. Lacidipine was also potent in protecting cells from the marked impairment of calcium homeostasis caused by oxidative stress induced by H2O2. Similarly, in the isolated rabbit heart electrolysis of the perfusion medium increases coronary artery pressure and this is antagonised by prior treatment with lacidipine. In vivo marked protection has been seen in animal models of vascular damage. In the stroke-prone spontaneously hypertensive rat lacidipine, at doses that do not block the development of hypertension, prevent mortality and tissue damage to brain and kidney, organs at risk in this model. Lacidipine also blocked the development of arterial lesions in two animal models of atherosclerosis the hypercholesterolaemic rabbit and the hypercholesterolaemic hamster. These actions can be at least partially ascribed to mechanisms other than simple blood pressure reduction and might well relate to antioxidant activity.