In vivo coronary effects of endothelin-1 after ischemia-reperfusion. Role of nitric oxide and prostanoids.
To examine the effects of reperfusion after short and prolonged ischemia on the coronary action of endothelin-1, left circumflex coronary artery flow was electromagnetically measured, and 15- or 60-min occlusion of this artery followed by reperfusion was induced in anesthetized goats. In non-treated animals, during reperfusion after 15-min occlusion, the duration but not the peak of endothelin-1-induced coronary effects (0.01-0.3 nmol) was increased, and the effects of acetylcholine (3-100 ng) were unchanged. During reperfusion after 60-min occlusion, the peak and duration of endothelin-1-induced effects were increased whereas those of acetylcholine were decreased. N(w)-nitro-L-arginine methyl esther (L-NAME) treatment did not modify the peak and duration of the coronary effects of endothelin-1 during reperfusion after both durations of occlusion. This treatment inhibited the effects of the two higher doses but not those of the two lower doses of acetylcholine during reperfusion after 15-min occlusion, and it did not modify the effects of any dose of this drug during reperfusion after 60-min occlusion. Meclofenamate treatment did not modify the coronary effects of endothelin-1 and acetylcholine during reperfusion after both durations of occlusion. These results suggest that ischemia-reperfusion increases the coronary response to endothelin-1, which is more pronounced during reperfusion after prolonged than after brief ischemia, and that this increased response is probably related to inhibition of nitric oxide release, without involvement of prostanoids.
Fernández
Nuria
N
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo 2, 28029, Madrid, Spain.
Martínez
María Angeles
MA
Climent
Belén
B
García-Villalón
Angel L
AL
Monge
Luis
L
Sanz
Elena
E
Diéguez
Godofredo
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006041:Goats; D006439:Hemodynamics / Q000187:drug effects; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester