M. Koshita et al., Pranidipine enhances relaxation produced by endothelium-derived relaxing factor in carotid artery, EUR J PHARM, 385(2-3), 1999, pp. 191-197
The effects of pranidipine, a novel dihydropyridine-type Ca2+-channel antag
onist, on acetylcholine-induced endothelium-dependent relaxation were inves
tigated in isolated carotid artery of the guinea-pig. In arteries contracte
d with high-K+ solution ([K+](0) = 28.8 mM) containing noradrenaline, the r
elaxation was inhibited by N-omega-nitro-L-arginine, indicating an involvem
ent of endothelium-derived relaxing factor. Pranidipine (10(-9)-10(-7) M) a
ugmented the relaxation in a concentration-dependent manner. Sodium nitropr
usside produced a relaxation in arteries contracted with high-K+ solution c
ontaining noradrenaline, in an endothelium-independent manner, and the rela
xation was enhanced by pranidipine. 1H-[1,2,4] oxadiazolo [4,3-a] quinoxali
n-1-one (ODQ), an inhibitor of nitric oxide-sensitive guanylate cyclase, at
tenuated the relaxation produced by acetylcholine or sodium nitroprusside.
In the presence of ODQ, pranidipine did not enhance the acetylcholine-induc
ed relaxation. The relaxation produced by endothelium-derived hyperpolarizi
ng factor was inhibited by pranidipine, with no alteration of the hyperpola
rization. Thus, pranidipine augments the nitric oxide-induced relaxation. p
ossibly by enhancing the mechanisms related to cyclic GMP. (C) 1999 Elsevie
r Science B.V. All rights reserved.