α-Isocubebene modulates vascular tone by inhibiting myosin light chain phosphorylation in murine thoracic aorta
Byeong Hyeok Ye1, Eun Jung Kim2, Seung Eun Baek1,2, Young Whan Choi3, So Youn Park2, and Chi Dae Kim1,2,*
1Department of Pharmacology, School of Medicine, Pusan National University, Yangsan 50612, 2Gene & Cell Therapy Research Center for Vessel-associated Diseases, Pusan National University, Yangsan 50612, 3College of Natural Resources & Life Sciences, Pusan National University, Miryang 50463, Korea
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α-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms, but the mechanism responsible for this activity has not been determined. To determine the role played by ICB on the regulation of vascular tone, we investigated the inhibitory effects of ICB on vascular contractile responses by adrenergic α-receptor agonists. In addition, we investigated the role on myosin light chain (MLC) phosphorylation and cytosolic calcium concentration in vascular smooth muscle cells (VSMC). In aortic rings isolated from C57BL/6J mice, ICB significantly attenuated the contraction induced by phenylephrine (PE) and norepinephrine (NE), whereas ICB had no effects on KCl (60 mM)-induced contraction. In vasculatures precontracted with PE, ICB caused marked relaxation of aortic rings with or without endothelium, suggesting a direct effect on VSMC. In cultured rat VSMC, PE or NE increased MLC phosphorylation and increased cytosolic calcium levels. Both of these effects were significantly suppressed by ICB. In conclusion, our results showed that ICB regulated vascular tone by inhibiting MLC phosphorylation and calcium flux into VSMC, and suggest that ICB has anti-hypertensive properties and therapeutic potential for cardiovascular disorders related to vascular hypertension.