Is nitrodihydropyridine-induced photorelaxation of vascular smooth muscle mediated by nitric oxide?
The 1,4-dihydropyridine nifedipine is an important cardiovascular drug used for the control of angina, hypertension and other vascular diseases. Dihydropyridine L-type Ca2+ channel activators and antagonists share many common structural and conformational features that allow them to bind to the same 1,4-dihydropyridine receptor. Certain activators and antagonists of the L-type Ca2+ channel can also photosensitive smooth muscle to the relaxant effects of UV light. The mechanism by which dihydropyridines induce photorelaxation has not been elucidated, but may involve degradation to release NO. Streptozotocin (STZ), BAY k 8644 and PN-202-791 were found to release similar amounts of NO upon photostimulation in vitro. However, STZ was a much less potent photorelaxant than were the two dihydropyridine, thus suggesting differing mechanisms of action. Furthermore, for NO release and photorelaxation, structure-activity studies indicate that a nitro group was required at the 3 position in the dihydropyridine ring. The financial support of the Medical Research Council of Canada is gratefully acknowledged.