Effect of ischemia duration and nitric oxide on coronary vasoconstriction after ischemia-reperfusion.
The effects of the duration of ischemia on coronary vasoconstriction after ischemia-reperfusion were analysed in rat hearts. After 15, 30 or 45 min of global zero-flow ischemia and 15 min reperfusion, the coronary response to endothelin-1 (10(-10)-10(-7) M) and the thromboxane A2 analogue 9,11-dideoxy-1a,9a-epoxymethanoprostaglandin F2alpha (U46691, 10(-8)-10(-6) M) was recorded. Vasoconstriction induced by endothelin-1 only increased after short 15 min periods of ischemia. In contrast, the vasoconstriction induced by U46619 remained unmodified by short ischemias but was reduced after longer periods of ischemia (30 and 45 min). Inhibition of nitric oxide synthesis with the Nw-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) augmented the vasoconstriction induced by endothelin-1 in non-ischemic hearts, but not following ischemia. Similarly, L-NAME increased the vasoconstriction induced by U46619 to a greater extent in non-ischemic hearts than following ischemia. These results suggest that ischemia-reperfusion inhibits nitric oxide production, causing an increased coronary response to endothelin-1 after brief ischemias. Longer ischemias may non-specifically inhibit coronary vasoconstriction and reduce nitric oxide production.
García-Villalón
Angel Luis
AL
Departamento de Fisiología, Facultad de Medicina, Universidad Autonoma, Arzobispo Morcillo 2, Madrid 28029, Spain. angeluis.villalon@uam.es
Amezquita
Yesika María
YM
Monge
Luis
L
Fernández
Nuria
N
Climent
Belén
B
Sánchez
Ana
A
Diéguez
Godofredo
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019332:Endothelin-1; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester