Prasan Ananth M, McCarron Hugh C K, Zhang Yi, Jeremy Richmond W
Department of Medicine, University of Sydney, Sydney, NSW 2006, Australia.
Heart Lung Circ. 2007 Aug;16(4):274-81. doi: 10.1016/j.hlc.2007.02.092. Epub 2007 Apr 8.
Nitric oxide (NO) may modulate myocardial ischaemia/reperfusion (I/R) injury, but effects of hypercholesterolaemia on myocardial NO release during I/R are unknown.
A NO-specific carbon fibre electrode continuously measured coronary sinus [NO] during 60 min low-flow ischaemia (1 ml/min) and 60 min free reperfusion (I/R) in isolated rabbit hearts. Experimental groups (n=7 per group) were control, L-arginine supplement (200 microM), N-nitro-L-arginine methyl ester (L-NAME) treatment (8 microM) and hypercholesterolaemic.
During early I, NO release decreased markedly in control (-1356+/-286 pmol/min/g) and L-arginine (-1972+/-172) groups, but less in L-NAME (-441+/-89) and hypercholesterolaemic (-602+/-164) groups (both p<0.01 vs. controls). No increase in NO release during I was seen in any group. After R, NO release increased above baseline in control (+2333+/-591 pmol/min/g) and L-arginine (+1048+/-278) groups and hypercholesterolaemic (+1100+/-478) (p<0.05 vs. pre-ischaemia each group). There was little increase in NO release in the L-NAME group (+436+/-247 pmol/min/g, p<0.05 vs. controls). In each group, myocardial NO release declined towards pre-ischaemic levels during 60 min R. Hearts treated with L-arginine had similar NO release but better functional recovery than controls (p<0.01). Treatment with L-NAME was also associated with better functional recovery than in controls or hypercholesterolaemic hearts.
Myocardial NO release declines rapidly during ischaemia, but increases above baseline during early reperfusion. Improved function after L-arginine treatment appears to be independent of effects upon NO release. Hypercholesterolaemia is associated with reduced myocardial NO release, under both baseline conditions and during ischaemia and reperfusion.
一氧化氮（NO）可能调节心肌缺血/再灌注（I/R）损伤，但高胆固醇血症对I/R期间心肌NO释放的影响尚不清楚。
在离体兔心脏60分钟低流量缺血（1毫升/分钟）和60分钟自由再灌注（I/R）期间，用NO特异性碳纤维电极连续测量冠状窦[NO]。实验组（每组n = 7）为对照组、补充L-精氨酸（200微摩尔）、N-硝基-L-精氨酸甲酯（L-NAME）处理（8微摩尔）和高胆固醇血症组。
在缺血早期，对照组（-1356±286皮摩尔/分钟/克）和L-精氨酸组（-1972±172）的NO释放明显减少，但L-NAME组（-441±89）和高胆固醇血症组（-602±164）减少较少（两组与对照组相比，p<0.01）。任何组在缺血期间均未见NO释放增加。再灌注后，对照组（+2333±591皮摩尔/分钟/克）、L-精氨酸组（+1048±278）和高胆固醇血症组（+1100±478）的NO释放高于基线水平（每组与缺血前相比，p<0.05）。L-NAME组的NO释放增加很少（+436±247皮摩尔/分钟/克，与对照组相比，p<0.05）。在每组中，再灌注60分钟期间心肌NO释放降至缺血前水平。用L-精氨酸处理的心脏具有相似的NO释放，但功能恢复比对照组更好（p<0.01）。用L-NAME处理也与比对照组或高胆固醇血症心脏更好的功能恢复相关。
心肌NO释放在缺血期间迅速下降，但在早期再灌注期间高于基线水平增加。L-精氨酸处理后功能改善似乎与对NO释放的影响无关。在基线条件以及缺血和再灌注期间，高胆固醇血症与心肌NO释放减少有关。
