Joyeux Marie, Arnaud Claire, Godin-Ribuot Diane, Demenge Pierre, Lamontagne Daniel, Ribuot Christophe
Laboratoire Stress Cardiovasculaires et Pathologies Associées, Faculté de Pharmacie, Domaine de la Merci, 38706 La Tronche, France.
Cardiovasc Res. 2002 Aug 15;55(3):619-25. doi: 10.1016/s0008-6363(02)00268-7.
We have investigated the involvement of the endocannabinoid system in the delayed cardioprotection conferred by heat stress preconditioning in the isolated rat heart.
Rats were divided into eight groups (n=7 in each group), subjected to either heat stress (42 degrees C for 15 min, HS groups) or sham anaesthesia (Sham groups). Twenty-four hours later, their hearts were isolated, retrogradely perfused, and subjected to a 30-min occlusion of the left coronary artery followed by 120 min of reperfusion. Some hearts were perfused with either SR 141716 (a cannabinoid CB(1) receptor antagonist, 1 microM), SR 144528 (a CB(2) receptor antagonist, 1 microM) or L-NAME (a NOS inhibitor, 3 microM) 5 min before ischaemia and during the ischaemic period.
The infarct size-reducing effect conferred by heat stress (35.7+/-1.8% in Sham to 14.1+/-0.6% in HS groups) was not altered by the perfusion of SR 141716 (11.2+/-1.5%) but was abolished by both SR 144528 (36.6+/-1.6%) and L-NAME (32.0+/-4.4%). In hearts from non-heat-stressed rats, perfusion with SR 141716 (32.8+/-1.6%), SR 144528 (33.4+/-2.2%) and L-NAME (31.6+/-2.9%) had no effect on infarct size.
These results suggest an involvement of endocannabinoids, acting through CB(2) receptors, and NO in the cardioprotection conferred by heat stress against myocardial ischaemia. The possible interaction between both mediators of the heat stress response remains to be determined.
我们研究了内源性大麻素系统在热应激预处理对离体大鼠心脏延迟性心脏保护作用中的参与情况。
将大鼠分为八组（每组n = 7），分别进行热应激（42℃，15分钟，热应激组）或假麻醉（假手术组）。24小时后，分离心脏，逆行灌注，然后左冠状动脉闭塞30分钟，再灌注120分钟。在缺血前5分钟和缺血期间，一些心脏用SR 141716（一种大麻素CB(1)受体拮抗剂，1μM）、SR 144528（一种CB(2)受体拮抗剂，1μM）或L-NAME（一种一氧化氮合酶抑制剂，3μM）灌注。
热应激带来的梗死面积减小效应（假手术组为35.7±1.8%，热应激组为14.1±0.6%）不受SR 141716灌注（11.2±1.5%）的影响，但被SR 144528（36.6±1.6%）和L-NAME（32.0±4.4%）消除。在非热应激大鼠的心脏中，用SR 141716（32.8±1.6%）、SR 144528（33.4±2.2%）和L-NAME（31.6±2.9%）灌注对梗死面积无影响。
这些结果表明，内源性大麻素通过CB(2)受体发挥作用，以及一氧化氮参与了热应激对心肌缺血的心脏保护作用。热应激反应的这两种介质之间可能的相互作用仍有待确定。
