Hyperoxic and hyperbaric-induced cardioprotection: Role of nitric oxide synthase 3

Objective: The relative contributions of the fraction of inspired oxygen (F1O2) and atmospheric pressure (ATM) to cardioprotection are unknown. We determined whether the product of F1O2 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% O-2 at 1 ATM), (2) hyperoxia + normobaria (100% O-2 at 1 ATM), (3) nonnoxia+hyperbaria (21% O-2 at 2 ATM) and (4) hyperoxia+hyperbaria (100% O-2 at 2 ATM). Results: Infarct size following 25 min ischemia and 180 min reperfusion was decreased following hyperoxia+non-nobaria and normoxia+ hyperbaria compared with normoxia+normobaria and further decreased following hyperoxia+hyperbaria treatment. L-NAME (200 mu M) 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. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.