Effects of Cicletanine on Histamine‐induced Contractions of Isolated Rabbit Mesenteric Arteries

Abstract

The antagonism by cicletanine of contractile responses to histamine has been examined in vitro on ring preparations of rabbit mesenteric arteries. Cicletanine (10(-8)-10(-6) M) caused a parallel rightward shift of histamine concentration response curve, with a pA2 value of 7.48 (slope = 0.89 +/- 0.19, not significantly different from unity). Histamine-induced contractions were nifedipine-sensitive and associated with cicletanine-sensitive increased 45Ca uptake. Endothelium removal resulted in enhanced contractile responses to histamine, but did not significantly modify cicletanine-induced antagonism: KB (dissociation constant) values for cicletanine antagonism in the presence or absence of endothelium were: 3.7 (+/- 0.1) X 10(-8) M and 3.6 (+/- 0.3) X 10(-8) M, respectively. Cicletanine (greater than 10(-4) M) also significantly attenuated 10 mM caffeine-induced contractions in rings exposed to Ca-free 100 mM K+ depolarizing medium. The results suggest that cicletanine-induced antagonisms of histamine H1 receptor-mediated contractions of rabbit mesenteric arteries is associated with interference with calcium entry as well as at high concentrations, release from intracellular stores.

In vitro vascular effects of cicletanine in pregnancy‐induced hypertension

“…The finding of unchanged cicletanine response following endothelium-removal, clearly shows that the mechanism of action of cicletanine is unrelated to the release of endothelium-derived relaxant factor(s). Comparable lack of endothelial factors in cicletanine-induced relaxation has been reported for rabbit mesenteric arteries (Ebeigbe et al, 1989).…”

“…The vascular effects of cicletanine, an antihypertensive fuorpyridine compound, have been described in a variety of animal (Malherbe et al, 1988;Auguet et al, 1988;Bukoski et al, 1989;Ebeigbe et al, 1989) and human (Schoeffter & Godfraind, 1988; smooth muscles. Cicletanine competitively antagonizes hisamine H -receptor-mediated contractions in the guinea-pig isolated ileum (Schoeffter et al, 1987), rabbit mesenteric artery (Ebeigbe et al, 1989), and human coronary, internal mammary artery and saphenous vein (Schoeffter & Godfraind, 1988;. Also, cicletanine-induced inhibition of contractile responses in rabbit mesenteric arterial and aortic smooth muscles (Ebeigbe et al, 1989) have been associated with interference with calcium metabolism within the vascular smooth muscle cells.…”

“…Cicletanine competitively antagonizes hisamine H -receptor-mediated contractions in the guinea-pig isolated ileum (Schoeffter et al, 1987), rabbit mesenteric artery (Ebeigbe et al, 1989), and human coronary, internal mammary artery and saphenous vein (Schoeffter & Godfraind, 1988;. Also, cicletanine-induced inhibition of contractile responses in rabbit mesenteric arterial and aortic smooth muscles (Ebeigbe et al, 1989) have been associated with interference with calcium metabolism within the vascular smooth muscle cells.…”