Coronary reactivity to endothelin-1 during partial ischemia and reperfusion in anesthetized goats. Role of nitric oxide and prostanoids.
To examine the coronary reactivity to endothelin-1 and its interaction with nitric oxide or prostanoids during partial coronary ischemia and reperfusion, left circumflex coronary artery flow was electromagnetically measured, and partial occlusion of this artery was induced for 60 min, followed by reperfusion in anesthetized goats (eight non-treated, six treated with N(w)-nitro-L-arginine methyl esther (L-NAME) and five treated with meclofenamate). During partial occlusion, coronary vascular conductance was reduced by 24-37% (P<0.01), and the coronary vasodilatation in response to acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) was much decreased in every case; the vasoconstriction in response to endothelin-1 (1-10 microg) was depressed in non-treated animals, and this depression was reversed by L-NAME and was accentuated by meclofenamate. At 30 min of reperfusion coronary vascular conductance remained decreased by 22-27% (P<0.01), and the vasodilatation in response to acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg), as well as the vasoconstriction with endothelin-1 (1-10 microg), were as in the control and comparable in the three groups of animals. These results suggest: (a) that during ischemia, the coronary vasodilator reserve is greatly reduced, and the vasoconstriction with endothelin-1 is blunted, with preservation of the modulatory role of nitric oxide and involvement of vasoconstrictor prostanoids in this vasoconstriction, and (2) that during reperfusion, the coronary vasodilator reserve and the coronary reactivity to acetylcholine and endothelin-1 recover, but the modulatory role of nitric oxide in this reactivity may be attenuated.
Fernández
Nuria
N
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo 2, 28029 Madrid, Spain.
Martínez
Maria 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; D003326:Coronary Circulation / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology; D019332:Endothelin-1 / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D005260:Female; D006041:Goats; D008469:Meclofenamic Acid / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester