Ken-ichi Yonemura

On the mode of action of ergometrine in the isolated dog coronary artery

Coronary vasoconstrictor responses to ergometrine were examined in spiral coronary arterial preparations of dogs. Either ergometrine or serotonin (5-HT) produced dose-dependent contractions of the strips. Methysergide significantly depressed the contractions induced by ergometrine or 5-Ht. Dihydroergotamine and phentolamine depressed constrictor responses to ergometrine, while phenoxybenzamine did not. The 5-HT antagonistic action of phentolamine was stronger than that of phenoxybenzamine. The results indicate that ergometrine may act on coronary arteries mainly through activation of 5-HT receptors.

Indomethacin-Induced Contractions of Dog Coronary Arteries

We investigated the mechanisms responsible for indomethacininduced contractions of coronary arteries. In isolated dog hearts perfused through the coronary circulation with blood under constant pressure, an intracoronary injection of 1 mg of indomethacin decreased coronary blood flow without significant changes in myocardial contractile force and heart rate. Indomethacin (10-8-10-5 M) caused concentration-dependent contractions of isolated dog coronary arterial strips. These contractions were significantly inhibited by calcium-free solution, diltiazem, nifedipine, prostaglandin E1, arachidonic acid, and phospholipase A2, but not by phenoxybenzamine, atropine, or oleic acid. Propranolol and prostaglandin F2α*** tended to enhance the contractions. The results indicate that indomethacin contracts dog coronary arteries through inhibition of intramural synthesis of vasodilating prostaglandins.

Effects of prostaglandin E1 on isolated dog renal artery

Actions of prostaglandin (PG) E1 were investigated using isolated dog renal arterial strips. Norepinephrine increased the tension of the renal arterial strips contracted with potassium, and this response was depressed by phentolamine. Isoproterenol produced relaxant effects on these arteries, and this response was converted to contractile one by propranolol. Diltiazem dose dependently relaxed the potassium-contracted strips. PGE1 (10(-9)-3 X 10(-8) Gm./ml.) constricted the renal arterial strips, while in higher concentrations (10(-7)-3 x 10(-7) Gm./ml.) it caused relaxations of them. Contractile responses by PGE1 were not affected by phentolamine or phenoxybenzamine, but were suppressed by diltiazem. On the other hand, relaxant effects of PGE1 were not changed by propranolol. Papaverine or theophylline significantly inhibited the contractions induced by PGE1. From these results it is suggested that (1) in the dog renal artery adrenergic alpha-receptors must be more dominant than beta-receptors; (2) PGE1 will produce a depolarization of renal arterial smooth muscle and/or increase an active transport of calcium ions into smooth muscle cells; and (3) the relaxant responses by PGE1 may be related to an increase in cellular cyclic adenosine monophosphate (AMP) contents.