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.