Coronary and aortic vasoreactivity protection with endothelin receptor antagonist, bosentan, after ischemia and hypoxia in aged rats

This study investigated the effects of bosentan, a dual endothelin ETA and ETB receptor antagonist, during hypoxia-reoxygenation of senescent aorta and during ischernia-reperfusion of senescent heart. Isolated aortic rings and isolated hearts from adult and senescent rats were submitted, respectively, to hypoxia/reoxygenation (20/30 min) and to low-flow ischemia/reperfusion (45/30 min), without or with bosentan (10(-5) M). In the aorta, bosentan treatment prevented the impairment of relaxation in response to acetylcholine after hypoxia-reoxygenation at both ages. In the heart, coronary flow recovery during reperfusion, which is lower in senescents than in adults (48% vs. 76% of baseline value, respectively; P < 0.05) was fully prevented by bosentan. Prevention of endothelial dysfunction during reoxygenation of hypoxic aorta and of coronary vasoconstriction during reperfusion of ischemic heart with a dual endothelin ETA and ETB receptor antagonist suggests a role of endothelin in the vulnerability of aorta to hypoxia-reoxygenation, and of coronary arteries to ischernia-reperfusion, especially during aging. (C) 2001 Elsevier Science B.V. All rights reserved.