Elevation of D‐glucose impairs coronary artery autoregulation after slight reduction of coronary flow

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Abstract
Diabetes mellitus is thought to increase the susceptibility of tissue to hypoxic injury through d‐glucose‐induced alterations of intracellular. metabolism. Therefore the effects of hyperglycaemia on coronary artery autoregulation under slight reduction of coronary flow were investigated 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) when L‐arginine as a precursor of the endothelium‐derived relaxing factor (EDRF/NO) was available and formation of prosta‐glandines was intact. Under high (44 mM) D‐glucose concentrations on the other hand, a sustained vasodi‐latation dependent on the availability of L‐arginine was observed, when formation of prostaglandins was blocked. This effect was partially reduced in the presence of prostaglandin synthesis. Furthermore, the effect of L‐arginine under both conditions could be antagonized by the L‐arginine‐analogue NAG‐nitro‐L‐arginine‐methyl‐ester (100 μm). Our results suggest that hyperglycaemia impairs coronary artery autoregulation by reducing the threshold for hypoxic vasodilatation in an EDRF/NO‐dependent manner. Concomitantly a shift from the formation of vaso‐dilatatory to vasoconstrictive prostaglandines was observed. These results might be of particular interest in patients with diabetes mellitus and ischaemic heart disease.