Hemodynamic, Antivasoconstrictor, and Antiatherosclerotic Effects of Calcium Antagonists in Animal Models of Atherosclerosis

Abstract

Calcium antagonists retard the development of atherosclerosis in cholesterol-fed rabbits and modestly enhance regression after their return to a normal diet. Proliferative lesions following endothelial damage (from, for example, balloon catheter, electrical stimulation) are also diminished. Many mechanisms for these effects have been proposed and their relative importance is not yet clear. However, changes in blood lipid levels do not play an important role. Only a few investigations into how atherosclerosis affects the hemodynamic actions of calcium antagonists have been carried out. Thus, the effects of isradipine were compared in atherosclerotic and normal rabbits. Isradipine increased heart rate and cardiac output less in atherosclerotic rabbits than in normal ones while having no effect on the surface electrocardiogram (ECG). In contrast, the arteriolar vasodilator, dihydralazine, induced ST-segment depression with similar falls in blood pressure, partly explainable by reflex tachycardia and intramyocardial maldistribution of coronary blood flow. Flow to the brain increased with isradipine and decreased with dihydralazine. In atherosclerotic animals, the pressor effects of norepinephrine, phenylephrine, and angiotensin II (Ang II) were amplified. Isradipine partly corrected this enhanced responsiveness. Calcium antagonists thus elicit beneficial hemodynamic and antivasoconstrictor effects in atherosclerotic experimental animals, in addition to having a long-term prophylactic antiatherosclerotic action.