PHARMACOLOGICAL CHARACTERISTICS OF A NEW CALCIUM-ANTAGONIST, MANIDIPINE - BENEFICIAL-EFFECTS ON RENAL CIRCULATION AND VASCULAR CHANGES

The calcium antagonist, manidipine, was developed on the basis of the hypothesis that antihypertensive drugs that act to improve renal hemodynamic alterations will be therapeutically beneficial in hypertensive patients. Manidipine shows long-lasting calcium channel-blocking action in vascular smooth muscle cells and antihypertensive actions in various types of hypertensive models. The drug has high selectivity for resistance vessels, dilates renal vasculature, and inhibits renal vascular constrictions induced by norepinephrine and angiotensin II in spontaneously hypertensive rats. It increases renal blood flow and has a prominent natriuretic action without changing glomerular filtration rate. The coronary dilating effect of the drug is similar to that of nifedipine, but its cardiodepressant effects are less potent than those of other dihydropyridines. Furthermore, manidipine prevents the development of cerebrovascular lesions and inhibits the progression of vascular damage in the brain and kidneys of stroke-prone spontaneously hypertensive rats. The drug also inhibits a proliferative response of the intima to balloon catheter-induced injury in the carotid arteries of spontaneously diabetic rats without affecting plasma lipids or blood pressure. These results suggest that manidipine may be useful for the treatment of hypertensive patients with or without vascular complications.