Naftidrofuryl inhibits contractions to serotonin in intact and de-endothelialized cerebral arteries in vitro.
Excised segments of rabbit middle cerebral artery were cannulated and perfused in vitro at constant flow (1 ml/min). In vessels with intact endothelium, integrity of the intima was checked by determining relaxations to acetylcholine. In another series of segments, the endothelium was destroyed mechanically. Serotonin (5-HT) was added to the perfusate in increasing concentrations (3 x 10(-10) to 10(-4) M). Perfusion pressure served as the index of vasomotor responses of the arterial segment. At therapeutic concentrations, the 5-HT2 antagonist naftidrofuryl did not change perfusion pressure of normal vessels in the absence of 5-HT. Addition of 5-HT to intact vessels had no effect on perfusion pressure, but potentiated the contraction induced by KCl. This reaction was greatly amplified after de-endothelialization. Addition of naftidrofuryl (10(-7) M) to the perfusate strongly inhibited 5-HT's contracting effects on both intact and deendothelialized arterial segments. Naftidrofuryl at 10(-6) M further displaced the dose-effect curve to the right in a competitive manner. These data confirm the potentiating effect of 5-HT on vascular smooth muscle (even in intact vessels) and the anticonstricting effects of naftidrofuryl when 5-HT2 receptors on smooth muscle cells are activated by serotonin.
Oudart
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Laboratoire de Pharmacologie, Faculté de Pharmacie, Limoges, France.
D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000502:physiology*; D008297:Male; D009257:Nafronyl / Q000494:pharmacology*; D011817:Rabbits; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D012702:Serotonin Antagonists; D009257:Nafronyl