Antithrombosis through activating endothelial target for acetylcholine and its molecular mechanism / 中国药理学通报

ABSTRACT

AIM To examine antithrombotic effects of arecoline on the arterial thrombosis induced by carrageenin in mice through modulating the functions of endothelium and determine its mechanisms from hemostatic system, the platelet aggregative functions and the bioactive factors released by vascular endothelial cells. METHODS Kappa carrageenin was given ip in mice and mice were fed at the temperature of 20 to 21 degrees and at the humidity of 30 percent to 50 percent. RESULTS On the foregoing models of thrombosis, arecoline could antagonize the formation of thrombosis through activating the endothelial target for acetylcholine in a dose dependent manner and its antithrombotic potency was 250 to 500 times greater than aspirin; while under the same conditions, pilocarpine could not antagonize the formation of thrombosis. The levels of TT, PT, KPTT and MAR had no prominent changes compaired with control groups. The levels of t-PA became higher greatly than normal and the levels of PAI 1 became lower greatly than normal 2 hours after intravenous injection of arecoline in rats. Arecoline could decrease the higher plasma levels of thromboxane A2 and increase the lower plasma levels of prostacyclin in a dose dependent manner in the mice tail thrombosis induced by carrageenin. CONCLUSION The antithrombotic effects of arecoline are associated with activating the endothelial target for acetylcholine closely, but are not associated with muscarinic receptors,and not relevant to hemostatic systems or functions of platelet aggregation directly.