Vasodilatation induced by pinacidil in dogs. Comparison with hydralazine and nifedipine.
In helical strips of dog arteries precontracted with prostaglandin (PG) F2 alpha, pinacidil and nifedipine produced a dose-related relaxation. The potencies of pinacidil were in the order of coronary and renal greater than mesenteric greater than basilar and middle cerebral arteries, whereas those of nifedipine were in the order of basilar and renal greater than mesenteric and coronary arteries. Pinacidil caused a greater relaxation in mesenteric veins than in the arteries. Hydralazine consistently relaxed the arteries only at 10(-3) M. In mesenteric artery strips exposed to Ca2+-free, high K+ media, contractions induced by Ca2+ were reduced by 10(-8) M nifedipine, but they were not influenced by 10(-5) M pinacidil or by 10(-4) M hydralazine. In the arteries exposed to Ca2+-free media and stimulated by PGF2 alpha or norepinephrine, tonic contractions induced by Ca2+ were reduced moderately by 10(-5) M pinacidil but only slightly by 10(-8) M nifedipine. In Ca2+-free media, PGF2 alpha-induced contractions were inhibited only by pinacidil. In isolated mesenteric vasculature, perfusion pressure was lowered by pinacidil and hydralazine. It may be concluded that pinacidil produces vasodilatation due to interference with the transmembrane influx of Ca2+ into smooth muscle evoked by receptor stimulation but not that due to inhibition in the Ca2+ influx associated with K+-induced membrane depolarization. Decreased release of Ca2+ from intracellularly stored sites or increased sequestration to the sites may also be involved. Pinacidil appears to dilate arteries and veins as well as resistance vessels, whereas hydralazine appears to act exclusively on resistance vessels.
Toda
N
N
Nakajima
S
S
Miyazaki
M
M
Ueda
M
M
D000818:Animals; D015237:Dinoprost; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006146:Guanidines / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D020110:Pinacidil; D011188:Potassium / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D006146:Guanidines; D011460:Prostaglandins F; D006830:Hydralazine; D020110:Pinacidil; D015237:Dinoprost; D009543:Nifedipine; D011188:Potassium; D009638:Norepinephrine