Differential sensitivity of proximal and distal coronary arteries to a nitric oxide donor following reperfusion injury or inhibition of nitric oxide synthesis.

ABSTRACT

OBJECTIVE: The effect of the nitric oxide donor, SIN-1, in proximal and distal coronary arteries with normal endothelium was characterised before and after inhibition of NO synthesis with L-nitroarginine methyl ester (L-NAME). The effect of reperfusion injury in vivo in similar vessels on the response to SIN-1 was also assessed. METHODS: In vitro reactivity of preconstricted coronary arterial rings was studied in control dogs (group 1), and dogs in which the left circumflex coronary artery was subjected in vivo to four acute occlusions of 5 min duration, with three intervening reperfusion periods of 5 min and a final reperfusion period of 60 min (group 2). The effects of acetylcholine and SIN-1 on the tone of left circumflex and left anterior descending coronary vascular rings were examined before and after treatment with L-NAME. RESULTS: Proximal [1851 (SEM 82) microns] and distal [477(19) microns] vessels were studied. In control dogs (group 1) acetylcholine caused relaxation in proximal and distal coronary arteries (p > 0.05). No difference in responsiveness of left circumflex or left anterior descending coronary arteries was observed in the control group. In group 2 the response to acetylcholine was significantly (p < 0.05) attenuated in left circumflex coronary arteries exposed to ischaemia and reperfusion compared with left anterior descending control rings from the same heart. Proximal vessels in group 1 and group 2 showed greater sensitivity to the vasodilator effects of SIN-1 than distal vessels. Proximal left circumflex vessels exposed to ischaemia and reperfusion showed enhanced sensitivity to the relaxant effects of SIN-1 compared to control proximal vessels obtained from the same hearts. Reperfusion was not associated with any alteration in sensitivity of distal vessels to SIN-1. Similarly, inhibition of the synthesis of endothelium derived relaxing factor (EDRF) by L-NAME resulted in an enhanced response to SIN-1 in proximal vessels only. CONCLUSIONS: Endothelium dependent vasodilatation is attenuated by ischaemia and reperfusion in both proximal and distal coronary arteries of the size studied. The response to direct nitric oxide donation (bypassing vascular endothelial synthesis of EDRF) is inhibited by a basal endothelial process present in proximal coronary arteries only. This inhibition is abolished following reperfusion injury or inhibition of NO synthesis.