Submitted on February 8, 2006
Accepted on March 31, 2006
Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure
Jonas Hink1*, Stephen R Thom2, Ulf Simonsen3, Inger Rubin4, and Erik Jansen5
1 The Centre of Head and Orthopaedics, Department of Anaesthesia, Hyperbaric Oxygen Treatment Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen OE, Denmark; Diving School, The Royal Danish Navy, Copenhagen K, Denmark; Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark
2 Department of Emergency Medicine, Institute for Environmental Medicine, University of Pennsylvania Medical Center, Philadelphia, United States
3 Department of Pharmacology, University of Aarhus, Aarhus C, Denmark
4 Department of Medical Biochemistry and Genetics, The Panum Institute, University of Copenhagen, Copenhagen N, Denmark
5 The Centre of Head and Orthopaedics, Department of Anaesthesia, Hyperbaric Oxygen Treatment Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen OE, Denmark
* To whom correspondence should be addressed. E-mail: hink{at}dadlnet.dk.
Accumulating evidence suggest that hyperbaric oxygen (HBO) stimulates neuronal nitric oxide synthase activity, but the influence on endothelial nitric oxide synthase (eNOS) activity and vascular nitric oxide (NO) bioavailability remains unclear. We here used a bioassay employing rat aortic rings to evaluate vascular NO bioavailability. HBO exposure to 2.8 atmospheres absolute (ATA) in vitro decreased acetylcholine relaxation. This effect remained unchanged despite treatment with superoxide dismutase-polyethylene glycol and catalase-polyethylene glycol, suggesting that the reduction in endothelium-derived NO bioavailability was independent of superoxide production. HBO induced contraction in vitro of resting aortic rings with and without endothelium, and these contractions were reduced by the nitric oxide synthase (NOS) inhibitor N
-Nitro-L-arginine (L-NNA). In addition, in vitro HBO attenuated the vascular contraction produced by noradrenaline, and this effect was reversed by L-NNA but not by endothelium-denudation. These findings indicate stimulation of extra-endothelial NO production during HBO. A radiochemical assay was used to assess NOS activity in rat aortic endothelial cells. The catalytic activity of eNOS in cell homogenates was not decreased by HBO, and in vivo HBO exposure to 2.8 ATA was without effect on eNOS activity and/or vascular NO bioavailability examined in vitro. We conclude that HBO reduces endothelium-derived NO bioavailability independent of superoxide production, and this effect seems not related to a decrease in eNOS catalytic activity. In addition, HBO increases the resting tone of rat aortic rings, and attenuates the contractile response to noradrenaline, by endothelium-independent mechanisms that involve extra-endothelial NO production.
