Impaired effect of endothelin-1 on coronary artery stiffness in type 2 diabetes

Aim We examined whether there is a differential effect of endothelin-A antagonism on coronary artery compliance in type 2 diabetes mellitus compared to non-diabetic patients. Patient and methods We examined 32 patients, 11 type 2 diabetes mellitus and 21 non-diabetic patients, with atherosclerotic epicardial arteries free of significant luminal stenoses. Intracoronary BQ-123 (6 μmol), an endothelin-A receptor antagonist, was infused over 20 min. The artery lumen area in the proximal arterial segment was measured at end diastole and end systole before and after BQ-123 administration using an intravascular ultrasound catheter. Calculations were made of normalized arterial compliance index, in mm Hg− 1 × 103 and of arterial stiffness index β. Results Pulse pressure and heart rate did not change after BQ-123. In type 2 diabetes mellitus, normalized compliance index decreased from 1.79 ± 1.36 at baseline to 1.29 ± 0.82 after BQ-123 administration, whereas in non-diabetic patients it increased from 2.10 ± 1.36 to 3.00 ± 2.07 (p < 0.05 versus baseline) (F = 6.39, p = 0.02). In type 2 diabetes mellitus, β index increased from 1.97 ± 0.53 to 2.46 ± 0.95, whereas in non-diabetic patients it decreased from 1.83 ± 0.95 to 1.63 ± 0.84 (F = 7.80, p = 0.009). Big endothelin-1 at baseline was correlated with the baseline β index (p < 0.0001, r = 0.68). Conclusions Big endothelin-1 is correlated with the coronary artery stiffness. The effect of endogenous endothelin-1 on coronary artery stiffness is impaired in type 2 diabetes mellitus. This may have important therapeutic implications with respect to the introduction of endothelin receptor antagonists as cardiovascular therapeutic agents.