Characteristics of coronary endothelial dysfunction in experimental diabetes

Objective: To study the influence of diabetes on the endothelium-dependent vasodilation in the coronary arterial bed. Methods: The effects of acetylcholine (ACh 2–36 pmol·kg−1; 18 nmol·l−1–9.8 μmol·l−1; 0.1–10 μmol·l−1), l-arginine (1 mmol·l−1) and sodium nitroprusside (1 nmol·l−1–100 μmol·l−1) were measured on coronary conductivity, vascular tone and cGMP release (RIA) in healthy and diabetic dogs. Results: ACh-mediated (in cumulative intra-arterial infusion) increase in coronary conductivity was reduced ( P <0.01) in the diabetic dogs in vivo, whereas no increase in cGMP release was observed in isolated diabetic coronaries ( P <0.05) which could not be enhanced by l-arginine ( P <0.05). Inhibition of cyclo-oxygenase after 20 min further impaired ( P <0.01) responsiveness to ACh in vivo and diminished the ACh response in isolated coronary strips of the diabetic dogs, but not in those of the controls. Relaxation in response to sodium nitroprusside was not altered by diabetes. Conclusions: Diminished vasodilation in diabetes is due to a defect in endothelial nitric oxide production and action. Vasodilating prostanoids do not sufficiently compensate this defect.