Role of NO/cGMP in the cardioprotective effects of intrathecal morphine preconditioning against myocardial ischemia-reperfusion injury in rats / 中国药理学通报

ABSTRACT

Aim To investigate the role of NO/cGMP in the cardioprotective effects of intrathecal morphine preconditioning against myocardial ischemia-reperfu-sion injury in rats. Method 54 Male Sprague-Dawley Rats were used to establish the model of intrathecal catheter placement. The rats were randomly assigned to 9 groups. SHAM (sham group), CON (control, sa-line) , ITMP ( intrathecal morphine preconditioning, 3μg·kg-1 ) , L-NAME+ITMP ( NO synthetase inhibi-tor,L-NAME ) , ODQ + ITMP ( guanylate cyclase in-hibitor, ODQ ) , KT5823 + ITMP ( PKG inhibitor, KT5823),L-NAME,ODQ,KT5823,6ratsineach group. ITMP were produced by three cycles of 5 min intrathecal injection of morphine and 5 min intermis-sion before myocardial ischemia, CON were achieved by intrathecal injection of saline in the same way, L-NAME+ITMP, ODQ +ITMP, KT5823 +ITMP were prepared by intrathecally administering L-NAME ( 30 nmol), ODQ(11 nmol) and KT5823(20 pmol) 10 minutes prior to ITMP respectively, L-NAME, ODQ, KT5823 worked as the control of inhibitors themselves respectively without ITMP. Subsequently, all rats were subjected to 30 min of left coronary artery occlusion followed by 2 h of reperfusion except the SHAM group. Myocardial infarct size, as a percentage of the AAR, was determined by 2 , 3 , 5-triphenyltetrazolium stai-ning. Results Compared with CON, the volumes of IS and IS/AAR were reduced in ITMP ( P <0.01 );the protective effects of ITMP were abolished by pre-treatment with L-NAME, ODQ and KT5823 ( P <0.01 );Conclusions NO/cGMP might be involved in the cardioprotective effect of intrathecal morphine pre-conditioning against myocardial ischemia and reperfu-sion injury in rats.