INVOLVEMENT OF THE L-ARGININE-NITRIC OXIDE PATHWAY IN HYPERGLYCEMIA-INDUCED CORONARY-ARTERY DYSFUNCTION OF ISOLATED GUINEA-PIG HEARTS

The effects of hyperglycaemia and L-arginine on flow-induced reduction of coronary artery resistance were investigated in isolated guinea pi g hearts. In the presence of indomethacin, hyperglycaemia caused an in crease in flow-induced vasodilatation (P < 0 . 05); Hyperosmotic contr ols failed to mimic this effect. Addition of L-arginine strongly enhan ced this effect. Addition of D-arginine failed to mimic the effects of L-arginine. The effect of L-arginine was abolished by co-administrati on of N-G-nitro-L-arginine. In the absence of indomethacin and L-argin ine, the effect of hyperglycaemia was blunted, suggesting the formatio n of vasoconstrictive prostanoids. Addition of L-arginine again result ed in a significant increase in flow-induced vasodilatation. In conclu sion our results suggest that increased flow-induced vasodilatation un der hyperglycaemic conditions depends on an adequate supply of L-argin ine to maintain sufficient formation of nitric oxide.