Abstract
PKC activation by phorbol 12, 13-dibutyrate (PDBu) shows inhibitory effects on phenylephrine (PE)-induced contractions in pregnant uterine arteries. We hypothesize that PDBu inhibits PE-induced increases of intracellular free Ca2+ concentration ([Ca2+]i). Uterine arteries were isolated from near term pregnant ewes. Vascular smooth muscle [Ca2+]i was measured simultaneously with muscle contraction in the same tissue loaded with Fura-2 by using a CAF-110 intracellular Ca2+ analyzer. PE-induced contraction and simultaneously measured [Ca2+]i were compared between before and after PDBu treatment. Compared with before PDBu treatment, both 0.1 and 1 μM PDBu produced a significant decrease in PE-induced contraction and completely blocked PE-induced increases of [Ca2+]i as indicated by no changes of Rf340/380. These results suggested that PKC activation in pregnant uterine artery plays an inhibitory role in α1-adrenoceptor-mediated contraction through blocking the availability of free Ca2+ to the contractile proteins. (Supported in part by NIH grants HL57787 and HD 31226)
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