Cardiovascular Effect And Mechanism Study Of Endogenous Cannabinoid Anandamide

Marijuana(Cannabis sativa) is a kind of herbage, which was used to cure disease 1,000 years ago. Marijuana has many active ingredients. People have a new knowledge of the medical value of cannabinoids due to the studies on molecular level in the past twenty years. The endocannabinoid anandamide has been shown to elicit depressor effects, bradycardia, vasorelaxation, inhibition of neurotransmission and antiarrhythmic effect. To study its cardiac responses and mechanism, we observed the effects of anandamide and its receptor antagonists on heart function of isolated rat hearts under normal perfusion and on NO content and NOS activity in rat 1eft ventricular heart by benzidine-fluorescence spectrophotometry.ObjectiveTo observe the pharmacological effects of anandamide on the heart of rat in vitro and on NO content and NOS activity in rat 1eft ventricular heart.MethodsLangendorff method was used to observe the pharmacological effects of anandamide on heart rate(HR), coronary flow(CF), coronary perfusion pressure (CPP),maximal rate of left ventricular developed pressure(+dp/dtmax), maximal rate of left ventricular decline pressure(-dp/dtmax),left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP) and left ventricular developed pressure(LVDP) among rats experimented on. NO content and NOS activity were measured by benzidine-fluorescence spectrophotometry. ResultsAnandamide decreased HR, CPP, +dp/dtmax, -dp/dtmax, LVSP, and LVDP. Anandamide increased LVEDP and CF. The selective CB1 receptor antagonist AM251(1μmol·L-1) blocked part of cardiac responses to anandamide. Another selective CB2 receptor antagonist AM630(1μmol·L-1) and the nitric oxide synthase inhibitor N-omega- nitro-L-arginine methyl ester (L-NAME) (100μmol·L-1) had no significant effect on cardiac responses to anandamide. Anandamide could increase the cNOS activity , inhibit the iNOS activity and stimulate the release of NO from the myocardium.ConclusionsAnandamide decreased the contractility of heart muscle and slowed down the heart rate, showing negative inotropic action and negative chronotropic action. Anandamide caused coronary vasodilatation and coronary flow increase. Cannabinoid CB2 receptors and endogenous NO probably do not mediate those cardiac responses to anandamide. It is likely that other novel sites mediate cardiac responses to anandamide. By regulating myocardial NOS isoenzyme activity, increasing the cNOS activity ,inhibiting the iNOS activity and stimulating the release of NO, anandamide may be play a role of myocardial protection and have a potential application prospect in therapy of myocardial ischemia and hypertension.