Submitted on August 5, 2002
Accepted on January 6, 2003
NO produced by endothelial NO synthase is a mediator ofdelayed preconditioning-induced endothelial protection
Karine LAUDE1, Julie FAVRE1, Christian THUILLEZ1, and Vincent RICHARD1*
1 Pharmacology, INSERM E9920, Rouen, France
* To whom correspondence should be addressed. E-mail: Vincent.Richard{at}univ-rouen.fr.
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 I/60 min R, 24 hours after sham surgery or cardiac preconditioning (1x2 min I/5 min R and 2x5 min I/5 min R). The non selective 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 I. Preconditioning prevented the R-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%), while 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, suggest that NO produced by eNOS is a mediator of delayed endothelial preconditioning
