NO produced by endothelial NO synthase is a mediator of delayed preconditioning-induced endothelial protection.
Preconditioning with brief periods of ischemia-reperfusion (I/R) induces a delayed protection of coronary endothelial cells against reperfusion injury. We assessed the possible role of nitric oxide (NO) produced during prolonged I/R as a mediator of this endothelial protection. Anesthetized rats were subjected to 20-min cardiac ischemia/60-min reperfusion, 24 h after sham surgery or cardiac preconditioning (1 x 2-min ischemia/5-min reperfusion and 2 x 5-min ischemia/5-min reperfusion). The nonselective NO synthase (NOS) inhibitor l-NAME, the selective inhibitors of neuronal (7-nitroindazole) or inducible (1400W) NOS, or the peroxynitrite scavenger seleno-l-methionine were administered 10 min before prolonged ischemia. Preconditioning prevented the reperfusion-induced impairment of coronary endothelium-dependent relaxations to acetylcholine (maximal relaxation: sham 77 +/- 3; I/R 44 +/- 6; PC 74 +/- 5%). This protective effect was abolished by l-NAME (41 +/- 7%), whereas 7-NI, 1400W or seleno-l-methionine had no effect. The abolition of preconditioning by l-NAME, but not by selective nNOS or iNOS inhibition, suggests that NO produced by eNOS is a mediator of delayed endothelial preconditioning.
Laude
Karine
K
Institut National de la Santé et de la Recherche Médicale E9920, Department of Pharmacology, Rouen University Medical School, France.
Favre
Julie
J
Thuillez
Christian
C
Richard
Vincent
V
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000033:anatomy & histology / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects; D004730:Endothelium, Vascular / Q000502:physiology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012645:Selenomethionine / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D016166:Free Radical Scavengers; D007191:Indazoles; D014665:Vasodilator Agents; D030421:Peroxynitrous Acid; D009599:Nitroprusside; D009569:Nitric Oxide; D012645:Selenomethionine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester