Comprehensive Study of Evodia rutaecarpa-induced Contraction on Blood Vascular in Vivo and in Vitro

AimEvodiae Fructus (fruit of Evodia rutaecarpa), a blood vessel activator, has been used, with headache, migraine, shock etc., for a long history in Chinese medical practice. However, previous studies supported the vessel relaxation and the potential action on cardiac and cerebral blood circulation of vessel contraction. The present study was designed to explore it effects on contraction and the relative mechanism.MethodsEvodiae Fructus was extracted by dialysis tubing (in diameter of 100 Dalton cutoff) and the effect of the evodia dialyzed (ED) (> 100 D) was studied in vivo and in vitro.ResultsED could dose-dependently promote the micro-cerebral blood flow in mice and induced the contraction of rat thoracic aorta at rest and phenylephrine pre-evoked state. Compared with the vasocontraction under 50 mmol·L−1 KCl, 250 mg·L−1 ED increased by 113%. The effect was inhibited by a-adrenergic receptor blocker phentolamine, instead of β-adrenergic receptor blocker propranolol, M-adrenaline receptor blocker atropine, and angiotensin II receptor blocker losartan. The depletion of extracellular calcium decreased the contraction induced by ED and the addition of L-type calcium ion channel antagonist (nicardipine), calcium ion channel activator (BAY-K8644) and potassium ion channel opener (pinacidil) significantly affected the contraction induced by ED. Selected inhibitors were used to investigate the possible mechanism of ED-induced vasocontraction. Inhibitors of myosin light chain kinase (MLCK), Rho-kinase (ROK) and inositol 1, 4, 5-triphosphate (IP3) receptor suppressed the effect of ED.ConclusionED induced Ca2+-dependent and Ca2+-independent contraction, the Ca2+ influx, a-adrenoceptor, ROK and IP3 receptor signal pathways and MLCK activation might be involved in the contractile process. These results suggested that Evodiae Fructus could increase the blood vessel contraction by the effect on calcium channel on the membrane.