Cinnamomi ramulus ethanol extract exerts vasorelaxation through inhibition of Ca2+ influx and Ca2+ release in rat aorta

Abstract

Contraction of vascular smooth muscle cells depends on the induction of cytosolic calcium ion (Ca2+) due to either Ca2+ influx through voltage-gated Ca2+ channels or to receptor-mediated Ca 2+ release from the sarcoplasmic reticulum. The present study investigated the vasorelaxation effect of Cinnamomi ramulus ethanol extract (CRE) and the possible mechanisms in rat aorta. CRE (0.1mg/mL) relaxed vasoconstriction induced by phenylephrine (PE; 1μM) and angiotensin II (5M). Preincubation with CRE significantly reduced the rat aortic contraction by addition of CaCl2 in Ca2+-free Krebs solution and FPL64176 (10μM). Pretreatment with nifedipine (100μM) or verapamil (1μM) significantly reduced the CRE-mediated vasorelaxation of PE-induced vascular contraction. In addition, CRE also relaxed the vascular contraction caused by m-3M3FBS (5μg/mL), but U73122 (10μM) significantly inhibited the vasorelaxation of PE precontracted aortic rings. Furthermore, CRE significantly reduced the magnitude of PE- and caffeine (30mM)-induced transient contraction. In vascular strips, CRE downregulated the expression levels of phosphorylated PLC and phosphoinositide 3-kinase elevated by PE or m-3M3FBS. These results suggest that CRE relaxes vascular smooth muscle through the inhibition of both Ca2+ influx via L-type Ca2+ channel and inositol triphosphate-induced Ca2+ release from the sarcoplasmic reticulum.