Myocardial Release of Nitric Oxide During Ischaemia and Reperfusion: Effects of l-Arginine and Hypercholesterolaemia

Aims

Nitric oxide (NO) may modulate myocardial ischaemia/reperfusion (I/R) injury, but effects of hypercholesterolaemia on myocardial NO release during I/R are unknown.

Methods

A NO-specific carbon fibre electrode continuously measured coronary sinus [NO] during 60min low-flow ischaemia (1ml/min) and 60min free reperfusion (I/R) in isolated rabbit hearts. Experimental groups (n=7 per group) were control, l-arginine supplement (200μM), N-nitro-l-arginine methyl ester (L-NAME) treatment (8μM) and hypercholesterolaemic.

Results

During early I, NO release decreased markedly in control (−1356±286pmol/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±591pmol/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±247pmol/min/g, p<0.05 vs. controls). In each group, myocardial NO release declined towards pre-ischaemic levels during 60min 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.

Conclusion

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.

Keywords: Atherosclerosis, Nitric oxide, Nitric oxide synthase, Ischaemia