Cinnamomi ramulus Ethanol Extract Exerts Vasorelaxation through Inhibition of Ca(2+) Influx and Ca(2+) Release in Rat Aorta

Contraction of vascular smooth muscle cells depends on the induction of cytosolic calcium ion (Ca(2+)) due to either Ca(2+) influx through voltage-gated Ca(2+) 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 (0.1 mg/mL) relaxed vasoconstriction induced by phenylephrine (PE; 1 μM) and angiotensin II (5 μM). Preincubation with CRE significantly reduced the rat aortic contraction by addition of CaCl(2) in Ca(2+)-free Krebs solution and FPL64176 (10 μM). Pretreatment with nifedipine (100 μM) or verapamil (1 μM) significantly reduced the CRE-mediated vasorelaxation of PE-induced vascular contraction. In addition, CRE also relaxed the vascular contraction caused by m-3M3FBS (5 μg/mL), but U73122 (10 μM) 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 Ca(2+) influx via L-type Ca(2+) channel and inositol triphosphate-induced Ca(2+) release from the sarcoplasmic reticulum.