Acute endothelin_A receptor antagonism improves coronary artery compliance in coronary artery disease patients

Endothelin (ET) exerts a tonic, stiffening effect on the common carotid artery in rats in vitro. This effect is mediated via the ET_A receptor. The aim of this study was to examine the acute effects of ET_A receptor antagonism on coronary artery compliance in humans. We examined 22 patients with stable angina after diagnostic coronary arteriography. Intracoronary BQ-123 (6µmol), an ET_A receptor antagonist (14 patients), or saline (8 patients), was infused in an artery without significant lesion over 20min. The artery lumen area in the proximal arterial segment was measured at end diastole and end systole before and after BQ-123 or saline administration using an intravascular ultrasound catheter. Calculations were made of absolute (in mm²/mmHg×10³) and normalized compliance index (in mmHg^-1×10³). Pulse pressure decreased from 64±21 to 61±17mmHg after BQ-123 administration and increased from 59±16 to 68±20mmHg after saline administration (F = 9.54, P = 0.006). The respective changes in absolute compliance index were from 24±18 to 39±25 and from 19±15 to 14±17 (F = 6.43, P = 0.02). Normalized compliance index changed from 2.5±2.0 to 3.6±2.4 and from 2.7±2.6 to 1.6±1.8 (F = 11.92, P = 0.002) respectively, in the two groups. Acute ET_A receptor antagonism improves coronary artery compliance in coronary artery disease patients.