Anti-Contractile Mechanism of Resveratrol in Non-Vascular Smooth Muscle Under α1Adrenoceptor Stimulation involves IP3 Receptor, Protein Kinase-C and NADPH Oxidase

Abstract

con-Abstract Reactive oxygen species (ROS) are products from enzymatic systems that are responsible for several biological disturbances when uncontrolled. Superoxide anion (O 2- ), increases intracellular calcium-regulated contractile/relaxation responses in smooth muscles. Activation of α1-adrenoceptors promotes these contractions through the Gq pathway involving protein kinase C (PKC) and calcium mobilization. It has been reported that Gq pathway is related to ROS production. It has also been shown that resveratrol (RESV), an antioxidant agent, decreases vascular smooth muscle contraction. The effect of RESV was not yet demonstrated in the anococcygeus smooth muscle contraction. Since ROS are present in rat anococcygeus smooth muscle and RESV has an antioxidant effect, the hypothesis for the current work is that the contractile response, under α1-adrenoceptor stimulation, can be decreased by RESV through decreasing ROS production related to the pathways of PKC and calcium mobilization. Thus, the aims were to investigate if the RESV interferes with the non-vascular smooth muscle contractile reactivity stimulated by the α1-adrenoceptor agonist, phenylephrine (PE) and to analyze its potential mechanisms. Anococcygeus smooth muscles were isolated from male Wistar rats and placed in organ baths to evaluate isometric tension. RESV enhanced the decreased contractions after incubation with α1-adrenoceptor and IP3-receptor (RIP3) antagonists as well as PKC and NADPH oxidase inhibitors. Under α1-adrenoceptor stimulation, the anococcygeus smooth muscle contractions are indeed related to the pathway of ROS production, involving inhibition of Ca 2+ mobilization, PKC activation and NADPH oxidase that are all sensitive to RESV.