ELEVATION OF D-GLUCOSE IMPAIRS CORONARY-ARTERY AUTOREGULATION AFTER SLIGHT REDUCTION OF CORONARY FLOW

Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through D-glucose-induced alterations of intracellul ar, metabolism. Therefore the effects of hyperglycaemia on coronary ar tery autoregulation under slight reduction of coronary flow were inves tigated in isolated perfused guinea-pig hearts. Under normal (10 mM) D -glucose concentrations coronary autoregulation was intact in response to a slight reduction of coronary flow (from 6 to 4.5 mL min(-1)) whe n L-arginine as a precursor of the endothelium-derived relaxing factor (EDRF/NO) was available and formation of prostaglandines was intact. Under high (44mM) D-glucose concentrations on the other hand, a sustai ned vasodilatation dependent on the availability of L-arginine was obs erved, when formation of prostaglandins was blocked. This effect was p artially reduced in the presence of prostaglandin synthesis. Furthermo re, the effect of L-arginine under both conditions could be antagonize d by the L-arginine-analogue N-G-nitro-L-arginine-methyl-ester (100 mu M). Our results suggest that hyperglycaemia impairs coronary artery a utoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO-dependent manner. Concomitantly a shift from the formation of vasodilatatory to vasoconstrictive prostaglandines was observed. Th ese results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.