SUSTAINED INHIBITION OF NITRIC-OXIDE BY N-G-NITRO-L-ARGININE IMPROVES MYOCARDIAL-FUNCTION FOLLOWING ISCHEMIA-REPERFUSION IN ISOLATED-PERFUSED RAT-HEART

被引:97
作者
NASEEM, SA
KONTOS, MC
RAO, PS
JESSE, RL
HESS, ML
KUKREJA, RC
机构
[1] VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DIV CARDIOPULM RES, MOLEC & CELLULAR CARDIOL LABS, RICHMOND, VA 23298 USA
[2] LONG ISL JEWISH MED CTR, NEW HYDE PK, NY 11042 USA
关键词
NITRIC OXIDE; ENDOTHELIUM-DERIVED RELAXING FACTOR; ARRHYTHMIA;
D O I
10.1016/S0022-2828(08)80038-7
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It has been postulated that nitric oxide (NO) can react with superoxide anion (. O-2(-)) to generate hydroxyl (. OH) radical. If this is correct, inhibition of NO synthesis could attenuate . OH radical mediated ischemia/reperfusion injury. Therefore we studied the effects of N-G-nitro-L-arginine (L-NNA), a competitive inhibitor of the NO synthase enzyme on ischemia/reperfusion injury in isolated perfused rat hearts. Three groups of rats (n=12-15) were studied, Group I: Untreated ischemia/reperfusion control (37.5 min of global ischemia followed by 20 min reperfusion); Group II: ischemia/reperfusion with 25 mu M N-G-nitro-L-arginine; and Group III: ischemia/reperfusion in the presence of L-NNA and 2 mM L-arginine. the substrate for NO synthase. Coronary now (in ml/min) and ventricular developed pressure, +dP/dt and -dP/dt were measured 5 min prior to ischemia and at the end of reperfusion. Baseline preischemic developed pressure was significantly lower in L-NNA perfused hearts than controls (76.8+/-5.9 v 97.6+/-2.9 mmHg, P<0.05). However, the developed pressure following reperfusion was significantly greater in L-NNA perfused hearts (57.4+/-7.4 v 20.8+/-6.4 mmHg in control). This protective effect was reversed by the addition of L-arginine. Preischemic coronary now was decreased significantly in the L-NNA group (6.4+/-0.5 ml/min) compared to controls (11.6+/-0.7 ml/min), The duration of sinus rhythm was significantly improved from 3.8+/-1.2 min in controls to 15.1+/-0.8 min in L-NNA perfused hearts. A corresponding significantly lower incidence of arrhythmias was observed (10.2+/-1.5 in ischemia/reperfusion group v 1.7+/-0.8 min with L-NNA). Again, hearts perfused with LNNA plus L-arginine had more arrhythmias and a shorter duration of sinus rhythm, The results show that despite the reduction of myocardial contractility and coronary flow prior to ischemia, L-NNA significantly preserved myocardial contractility and reduced arrhythmias following reperfusion. Electron spin resonance or cytochrome c reduction assay demonstrated that L-NNA did not scavenge . OH nor . O-2(-) radical directly. These results suggest that ischemia/reperfusion injury observed in this model may in part be due to . OH radical formed as a result of NO interaction with . O-2(-) and that inhibition of this pathway by L-NNA leads to recovery of myocardial function.
引用
收藏
页码:419 / 426
页数:8
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