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 ET(A) and ET(B) receptor antagonist, during hypoxia-reoxygenation of senescent aorta and during ischemia-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 ET(A) and ET(B) receptor antagonist suggests a role of endothelin in the vulnerability of aorta to hypoxia-reoxygenation, and of coronary arteries to ischemia-reperfusion, especially during aging.
Besse
S
S
Laboratoire de Physiopathologie Cellulaire Cardiaque, ESA CNRS 5077, Université Joseph Fourier, Grenoble, France. Sophie.Besse@chups.jussieu.fr
Tanguy
S
S
Riou
B
B
Boucher
F
F
Bulteau
A L
AL
Le Page
C
C
Swynghedauw
B
B
de Leiris
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D000077300:Bosentan; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D065128:Endothelin Receptor Antagonists; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D010656:Phenylephrine; D000109:Acetylcholine; D000077300:Bosentan; D010100:Oxygen