[Show abstract][Hide abstract] ABSTRACT: Endogenous retinoic acid may play a role in inducing smooth muscle differentiation in the fetal ductus arteriosus. Maternal administration of retinoic acid may accelerate the process. This study was designed to investigate the effect of vitamin A on developmental changes in the contractile system of the ductus. Vitamin A was injected into pregnant rats and the ductus was isolated from the fetus at 19, 20, or 21 d of gestation. The fetus at 19 d of gestation served as a model of the preterm fetus. The force of contraction and [Ca]i were measured. Membrane depolarization caused by high KCl induced ductal contraction in all age groups studied. In the 19-d fetus, O2 did not cause significant contraction or changes in [Ca]i in the control group, but it did induce a significant contraction and increases in [Ca]i in the vitamin A-treated group. In the 20- and 21-d fetuses, 5% O2-induced contraction in the vitamin A-treated group was significantly greater than in the control group. In the 19-d fetus, noradrenaline-induced contraction and increases in [Ca]i, indicators of the size of the intracellular Ca pool, were observed and they were similar in the control group and in the vitamin A-treated group. These data suggest that 1) in the preterm fetus, the contractile system, including membrane depolarization, [Ca]i increase, and its activation of contractile proteins, is already functioning, but the O2-sensing mechanism is underdeveloped, 2) vitamin A accelerates the development of the O2-sensing mechanism of the ductus arteriosus.
Pediatric Research 07/2001; 49(6):747-54. · 2.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Effects of dehydrocurdione, a zedoary-derived sesquiterpene, on smooth muscle were investigated by recording the mechanical activity of intestines and aorta from guinea pigs and rats. Dehydrocurdione (0.1-3 mM) induced a sustained relaxation of rat duodenum and inhibited spontaneous motility. Dehydrocurdione (0.1-1 mM) inhibited the contractile response of guinea pig ileum induced by acetylcholine (0.01-10 microM), histamine (0.03-10 microM) and substance P (0.1-30 nM) in a non-competitive manner. Acetylcholine (0.5 microM) elicited a transient contraction followed by a sustained contraction of guinea pig ileum, and dehydrocurdione pretreatment inhibited the sustained component, which depends on Ca(2+) entry from the extracellular space. The high K(+)-induced contraction of rat aortic ring is reported to be blocked by Ca(2+) channel blockers, while the norepinephrine-induced contraction includes a Ca(2+) channel blocker-resistant component. Dehydrocurdione (1 mM) blocked the high K(+) (60 mM)-induced contraction of rat aortic ring by 81%, while it inhibited the norepinephrine (1 microM)-induced contraction by only 28%. Dehydrocurdione (1 mM) significantly reduced the high K(+)-stimulated increase in cytosolic Ca(2+) level of Fura-2-loaded mesenteric artery from rats. These results suggest that the inhibitory effects of dehydrocurdione on intestinal and vascular smooth muscle are mediated by blockade of Ca(2+) entry from the extracellular space.
European Journal of Pharmacology 10/2000; 403(3):235-42. · 2.59 Impact Factor