Hyperoxic and hyperbaric-induced cardioprotection: role of nitric oxide synthase 3.
OBJECTIVE
The relative contributions of the fraction of inspired oxygen (FIO2) and atmospheric pressure (ATM) to cardioprotection are unknown. We determined whether the product of FIO2 x ATM (oxygen partial pressure) controls the extent of hyperoxic+hyperbaric-induced cardioprotection and involves activation of nitric oxide synthase (NOS).


METHODS
Adult Sprague Dawley rats (n = 10/gp) were treated for 1 h with (1) normoxia+normobaria (21% O2 at 1 ATM), (2) hyperoxia+normobaria (100% O2 at 1 ATM), (3) normoxia+hyperbaria (21% O2 at 2 ATM) and (4) hyperoxia+hyperbaria (100% O2 at 2 ATM).


RESULTS
Infarct size following 25 min ischemia and 180 min reperfusion was decreased following hyperoxia+normobaria and normoxia+hyperbaria compared with normoxia+normobaria and further decreased following hyperoxia+hyperbaria treatment. l-NAME (200 microM) reversed the cardioprotective effects of hyperoxia+hyperbaria. Nitrite plus nitrate content was increased 2.2-fold in rats treated with normoxia+hyperbaria and hyperoxia+hyperbaria. NOS3 protein increased 1.2-fold and association of hsp90 with NOS3 four-fold in hyperoxic+hyperbaric rats.


CONCLUSIONS
Cardioprotection conferred by hyperoxia+hyperbaria is directly dependent on oxygen availability and mediated by NOS.
Cabigas
Bernadette P
BP
Division of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA. bgcab@yahoo.com
Su
Jidong
J
Hutchins
William
W
Shi
Yang
Y
Schaefer
Richard B
RB
Recinos
René F
RF
Nilakantan
Vani
V
Kindwall
Eric
E
Niezgoda
Jeffrey A
JA
Baker
John E
JE
D000818:Animals; D004789:Enzyme Activation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006931:Hyperbaric Oxygenation; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000737:chemistry*; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D018841:HSP90 Heat-Shock Proteins; D009566:Nitrates; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D010100:Oxygen