The focus of this grant proposal is to test the hypothesis that exposure to elevated 02 partial pressures, and to hyperbaric oxygen in particular, will increase the steady state concentration of nitric oxide (NO) in vivo.
The specific aims relate to evaluation of the biochemical and physiological events associated with ventilation using elevated partial pressures of 02. Studies will be performed with rats and isolated, perfused rat lung preparations. There are two specific aims for this proposal: (1) Investigate the in vivo potential mechanism(s) for increases in NO production due to O2 exposures by evaluating (a) elevations in stable products of' NO found in blood and he impact of potentially inhibitory pharmacological agents; (b) measuring O2-mediated changes in brain -NO concentration and their relation to blood flow, and (c) determine -NO-mediated inhibition of circulating blood neutrophil adhesion and also markers of oxidative stress. The second specific aim is to evaluate mechanisms for O2-dependent elevations in NO production using isolated, perfused lung preparations. The two sub-aims are: (a) To investigate variations in NO production due to pharmacological agents and changes in perfusion rates, and (b) To evaluate the role of calcium and other molecular mechanisms for alterations in 'NO production. We hypothesize that vasoconstriction mediated by elevated O2 partial pressures increases endothelial shear stress and this is the proximal stimulus for activation of nitric oxide synthase. The research plan is aimed to test this hypothesis and to look for alternative or additional mechanisms that may influence O2-induced responses.
| Elzarrad, Khair; Haroon, Abu; Reed, Darla et al. (2009) Early incorporated endothelial cells as origin of metastatic tumor vasculogenesis. Clin Exp Metastasis 26:589-98 |
| Elzarrad, M Khair; Haroon, Abu; Willecke, Klaus et al. (2008) Connexin-43 upregulation in micrometastases and tumor vasculature and its role in tumor cell attachment to pulmonary endothelium. BMC Med 6:20 |
| Han, Shih-Tsung; Bhopale, Veena M; Thom, Stephen R (2007) Xanthine oxidoreductase and neurological sequelae of carbon monoxide poisoning. Toxicol Lett 170:111-5 |
| Evans, Sydney M; Du, Kevin L; Chalian, Ara A et al. (2007) Patterns and levels of hypoxia in head and neck squamous cell carcinomas and their relationship to patient outcome. Int J Radiat Oncol Biol Phys 69:1024-31 |
| Jain, Deepika; Atochina-Vasserman, Elena; Kadire, Helchem et al. (2007) SP-D-deficient mice are resistant to hyperoxia. Am J Physiol Lung Cell Mol Physiol 292:L861-71 |
| Buerk, Donald G (2007) Nitric oxide regulation of microvascular oxygen. Antioxid Redox Signal 9:829-43 |
| Thom, Stephen R; Bhopale, Veena M; Velazquez, Omaida C et al. (2006) Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol 290:H1378-86 |
| Hink, Jonas; Thom, Stephen R; Simonsen, Ulf et al. (2006) Vascular reactivity and endothelial NOS activity in rat thoracic aorta during and after hyperbaric oxygen exposure. Am J Physiol Heart Circ Physiol 291:H1988-98 |
| Thom, S R; Fisher, D; Stubbs, J M (2006) Platelet function in humans is not altered by hyperbaric oxygen therapy. Undersea Hyperb Med 33:81-3 |
| Thom, Stephen R; Bhopale, Veena M; Fisher, Donald (2006) Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicol Appl Pharmacol 213:152-9 |
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