Influence of experimental diabetes on the mechanical responses of canine coronary arteries: role of endothelium

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Abstract
The influence of experimental diabetes on the endothelium mediated relaxation and contractile responses of canine isolated coronary arteries was studied in arteries removed from alloxan treated diabetic (280 mmol·kg−1) and control mongrel dogs. Strips with and without endothelium were suspended in Krebs bicarbonate solution for isometric recording. Relaxation responses to acetycholine (1.8 × 10−8 to 9.4 × 10−6 mol·litre−1, A23187 (10−8 to 1.28 × 10−6 mol·litre−1), and sodium nitroprusside (10−9 to 10−7 mol·litre−1) as well as contractile responses to prostaglandin F2a, (1.7 × 10−7to5.6 × 10−4 mol·litre−1) were determined. In all intact strips acetycholine, and A23187 induced similar concentration dependent reduction of the prostaglandin F2α (2 × 106 mol·litre−1) evoked tone. No significant difference was observed between sodium nitroprusside evoked relaxations of normal and diabetic arteries. Cyclooxygenase blockade reduced the maximal relaxations induced by acetylcholine and A23187 in diabetic vessels, whereas it did not change die endothelium dependent relaxation of normal arteries. Diabetes increased significantly the sensitivity to acetycholine (EC50 4.1(0.4) × 10−7 mol·litre−1 in control and 6(0.7) × 10−8 mol·litre−1 in diabetic arteries; p50:7(1) × 10−8 mol·litre−1 in control and 3.8(0.3) × 10−8 mol·litre−1 in diabetic vessels; p2α remained an equiactive constrictor in normal and diabetic vessels with intact endothelium. Endothelium removal abolished the relaxation responses to acetycholine and A23187 and considerably (p2α. The maximum tension induced by prostaglandin F2α was greater in diabetic denuded arteries (1.82(0.02) × 104 N·m−2) than in non-diabetic denuded vessels (1.25(0.04) × 104 N·m−2; p2α. They further suggest that the maintenance of sufficient relaxation capacity of diabetic dog coronary arteries requires the integrated operation of both endothelium derived relaxing factor and cyclooxygenase products (probably prostacyclin).