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 micromol), 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) x 10(3) and of arterial stiffness index beta.

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, beta 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 beta 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.