CHARACTERISTICS OF CORONARY ENDOTHELIAL DYSFUNCTION IN EXPERIMENTAL DIABETES

Objective: To study the influence of diabetes on the endothelium-depen dent vasodilation in the coronary arterial bed. Methods: The effects o f acetylcholine (ACh 2-36 pmol.kg(-1). 18 nmol.l(-1) -9.8 mu mol.l(-1) ; 0.1-10 mu mol.l(-1)), L-arginine (1 mmol.l(-1)) and sodium nitroprus side(1 nmol.1(-1) -100 mu mol.1(-1))were measured on coronary conducti vity, vascular tone and cGMP release (RTA) in healthy and diabetic dog s. Results: ACh-mediated (in cumulative intra-arterial infusion) incre ase in coronary conductivity was reduced (P < 0.01) in the diabetic do gs in vivo, whereas no increase in cGMP release was observed in isolat ed diabetic coronaries (P < 0.05) which could not be enhanced by L-arg inine (P < 0.05). inhibition of cyclo-oxygenase after 20 min further i mpaired (P < 0.01) responsiveness to ACh in vivo and diminished the AC h response in isolated coronary strips of the diabetic dogs, but not i n those of the controls. Relaxation in response to sodium nitroprussid e was not altered by diabetes. Conclusions: Diminished vasodilation in diabetes is due to a defect in endothelial nitric oxide production an d action. Vasodilating prostanoids do not sufficiently compensate this defect.