Prophylactic effects of an N- and L-type Ca2+ antagonist, cilnidipine, against cardiac hypertrophy and dysfunction in stroke-prone, spontaneously hypertensive rats.

To clarify the beneficial effects of cilnidipine, an L- and N-type calcium channel blocker, which were clinically observed against diastolic dysfunction in hypertrophied hearts of hypertensive patients, we investigated the effects of cilnidipine on cardiac remodeling and enhanced gene expression in stroke-prone, spontaneously hypertensive rats in comparison with that of captopril, a well-known angiotensin-converting enzyme inhibitor, at threshold doses with little blood pressure lowering effect. The expression of type III collagen and beta/alpha-myosin heavy chain as well as transforming growth factor-beta, and basic fibroblast growth factor were suppressed by both treatments, indicating the prevention or amelioration of cardiac dysfunction. Such beneficial effects were much more intense with cilnidipine treatment than in captopril. These results indicate that Ca2+ is a key factor in the pathogenesis of cardiac remodeling in hypertension. One possible beneficial effect of cilnidipine in the prevention of cardiac dysfunction may be due to the decreased amount of growth factors such as transforming growth factor-beta and basic fibroblast growth factor via direct action for Ca2+ influx and also via inhibition of local renin-angiotensin system in the myocardium.