Role of NO-cGMP-PKG signal transduction pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the role of nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signal transduction pathway in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.Methods Forty-eight male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications,weighing 250-350 g,were randomly assigned into 8 groups (n =6 each)normal saline group (NS group),morphine postconditioning group (Mp group),1-NG-nitroarginine methyl ester (L-NAME,NO synthase inhibitor) + morphine postconditioning group (L-NAME + MP group),ODQ (guanylate cyclase inhibitor) + morphine postconditioning group (ODQ + MP group),KT5823 (PKG inhibitor) + morphine postconditioning group (KT5823 + MP group),L-NAME group,ODQ group and KT5823 group.Myocardial ischemia was induced by 30 min of occlusion of anterior descending branch of left coronary artery followed by 2 h of reperfusion.At 25 rin of ischemia,normal saline 10 μl was intrathecally infused over 5 min in group NS,and morphine (3 μg/kg,10 μl) was intrathecally infused over 5 min in group MP.L-NAME (30 nmol,10 μl),ODQ (11 nmol,10 μl) and KT5823 (20 pmol,10 μl) were intrathecally injected at 10 rin before morphine postconditioning in L-NAME + MP,ODQ + MP and KT5823 + MP groups,respectively.Before myocardial ischemia (T0),at 25 and 30 min of ischemia (T1-2),and at 120 min of reperfusion (T3),MAP and HR were recorded,and rate-pressure product (RPP) was calculated.The rats were sacrificed at T3,and myocardial specimens were obtained for determination of myocardial infarct size as a percentage of area at risk (IS/AAR).Results MAP,HR and RPP were significantly lower at T1-3 than at T0 in each group.Compared with group NS,MAP was significantly increased at T3,and IS/AAR ratio was decreased in MP group,and no significant changes were found in the other groups.Compared with group MP,IS/AAR ratio was significantly increased in L-NAME + MP,ODQ + MP and KT5823 + MP groups,and no significant changes were found in the other groups.Conclusion NO-cGMP-PKG signal transduction pathway plays an important role in mitigation of myocardial ischemia-reperfusion injury by intrathecal morphine postconditioning in rats.