TY - JOUR T1 - Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure JF - Heart JO - Heart SP - 914 LP - 919 DO - 10.1136/hrt.2004.040386 VL - 91 IS - 7 AU - S J Leslie AU - J C S Spratt AU - S P McKee AU - F E Strachan AU - D E Newby AU - D B Northridge AU - M A Denvir AU - D J Webb Y1 - 2005/07/01 UR - http://heart.bmj.com/content/91/7/914.abstract N2 - Objective: To investigate the potential differential effects of selective endothelin (ET) A and dual ET-A/B receptor blockade in patients with chronic heart failure. Methods: Nine patients with chronic heart failure (New York Heart Association class II–III) each received intravenous infusions of BQ-123 alone (selective ET-A blockade) and combined BQ-123 and BQ-788 (dual ET-A/B blockade) in a randomised, placebo controlled, three way crossover study. Results: Selective ET-A blockade increased cardiac output (maximum mean (SEM) 33 (12)%, p < 0.001) and reduced mean arterial pressure (maximum −13 (4)%, p < 0.001) and systemic vascular resistance (maximum −26 (8)%, p < 0.001), without changing heart rate (p  =  0.38). Dual ET-A/B blockade significantly reduced the changes in all these haemodynamic variables compared with selective ET-A blockade (p < 0.05). Selective ET-A blockade reduced pulmonary artery pressure (maximum 25 (7)%, p  =  0.01) and pulmonary vascular resistance (maximum 72 (39)%, p < 0.001). However, there was no difference between these effects and those seen with dual ET-A/B blockade. Unlike selective ET-A blockade, dual ET-A/B blockade increased plasma ET-1 concentrations (by 47 (4)% with low dose and 61 (8)% with high dose, both p < 0.05). Conclusions: While there appeared to be similar reductions in pulmonary pressures with selective ET-A and dual ET-A/B blockade, selective ET-A blockade caused greater systemic vasodilatation and did not affect ET-1 clearance. In conclusion, there are significant haemodynamic differences between selective ET-A and dual ET-A/B blockade, which may determine responses in individual patients. ER -