Cinnamomi ramulus Ethanol Extract Exerts Vasorelaxation through Inhibition of Ca2+ Influx and Ca2+ Release in Rat Aorta

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 Ca2+ 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 (0.1 mg/mL) relaxed vasoconstriction induced by phenylephrine (PE; 1 mu M) and angiotensin II (5 mu M). Preincubation with CRE significantly reduced the rat aortic contraction by addition of CaCl2 in Ca2+-free Krebs solution and FPL64176 (10 mu M). Pretreatment with nifedipine (100 mu M) or verapamil (1 mu M) significantly reduced the CRE-mediated vasorelaxation of PE-induced vascular contraction. In addition, CRE also relaxed the vascular contraction caused by m-3M3FBS (5 mu g/mL), but U73122 (10 mu M) significantly inhibited the vasorelaxation of PE precontracted aortic rings. Furthermore, CRE significantly reduced the magnitude of PE-and caffeine (30 mM)-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.