iNOS is a mediator of the heat stress-induced preconditioning against myocardial infarction in vivo in the rat.
OBJECTIVE
The inducible isoform of nitric oxide synthase (iNOS) is known to be a trigger of the heat stress (HS)-induced cardioprotection. Since iNOS also appears to mediate various forms of myocardial preconditioning, the goal of this study was to investigate its role as a mediator of the HS response.


RESULTS
Male Wistar rats were divided in six groups, subjected or not to HS (42 degrees C internal temperature, for 15 min). Twenty-four hours later, they were treated or not with either L-NAME, a non-selective inhibitor of NO synthase isoforms, or 1400W, a selective iNOS inhibitor, 10 min before being subjected to a 30-min left coronary artery occlusion followed by a 120-min reperfusion, in vivo. The infarct size (tetrazolium staining) reducing effect conferred by heat stress (from 46.0+/-1.4% in sham to 26.8+/-3.8% in HS groups) was completely abolished by both L-NAME (53.9+/-3.1%) and 1400W (51.8+/-3.3%). Additional studies using Western blot analysis demonstrated a 3.8-fold increase in myocardial iNOS protein expression 24 h after HS.


CONCLUSIONS
These results suggest an involvement of iNOS as a mediator of the protection conferred by heat stress against myocardial ischaemia.
Arnaud
Claire
C
Laboratoire Stress Cardiovasculaires et Pathologies Associées, Faculté de Pharmacie, Domaine de la Merci, La Tronche, France.
Godin-Ribuot
Diane
D
Bottari
Serge
S
Peinnequin
André
A
Joyeux
Marie
M
Demenge
Pierre
P
Ribuot
Christophe
C
D000578:Amidines / Q000494:pharmacology; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D006358:Hot Temperature; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017208:Rats, Wistar
D000578:Amidines; D001596:Benzylamines; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019331:NG-Nitroarginine Methyl Ester