This grant proposes important laboratory studies of the mechanisms of action and toxicology of inhaled nitric oxide (NO). Our laboratory has reported that inhaling low levels of nitric oxide is a selective pulmonary vasodilator that reverses hypoxic pulmonary vasoconstriction. NO has mixtures were used to resuscitate hypoxic newborn sheep and treat diffuse acute lung injury. Inhaling nitric oxide improves the matching of pulmonary ventilation with perfusion in the Adult Respiratory Distress Syndrome (ARDS). Inhaled NO is also a rapid and profound bronchodilator in animal models. This grant proposes laboratory studies to examine the interaction of endogenous and exogenous pulmonary NO production, and to learn whether NO synthase inhibitors can augment the beneficial effects of NO inhalation in septic lung injury. In hypoxic newborn sheep the effects of respiratory and metabolic acidosis on NO induced pulmonary vasodilation will be explored. In guinea pigs the effects of NO will be examined on airway tone augmented by inflammatory stimuli (leukotrienes). A careful pathological analysis will be undertaken searching for any toxic effects of inhaling NO for periods up to one month upon normal adult and newborn rat lungs. In this manner our understanding will be enhanced of the safety of NO inhalation as a therapeutic agent in states of bronchospasm, pulmonary vasoconstriction, and diffuse acute pulmonary inflammation.
| Vaporidi, Katerina; Vergadi, Eleni; Kaniaris, Evangelos et al. (2012) Pulmonary microRNA profiling in a mouse model of ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 303:L199-207 |
| Steinbicker, Andrea U; Liu, Heling; Jiramongkolchai, Kim et al. (2011) Nitric oxide regulates pulmonary vascular smooth muscle cell expression of the inducible cAMP early repressor gene. Nitric Oxide 25:294-302 |
| Petersen, Bodil; Austen, K Frank; Bloch, Kenneth D et al. (2011) Cysteinyl leukotrienes impair hypoxic pulmonary vasoconstriction in endotoxemic mice. Anesthesiology 115:804-11 |
| Yu, Binglan; Shahid, Mohd; Egorina, Elena M et al. (2010) Endothelial dysfunction enhances vasoconstriction due to scavenging of nitric oxide by a hemoglobin-based oxygen carrier. Anesthesiology 112:586-94 |
| Vaporidi, Katerina; Francis, Roland C; Bloch, Kenneth D et al. (2010) Nitric oxide synthase 3 contributes to ventilator-induced lung injury. Am J Physiol Lung Cell Mol Physiol 299:L150-9 |
| Buys, Emmanuel S; Cauwels, Anje; Raher, Michael J et al. (2009) sGC(alpha)1(beta)1 attenuates cardiac dysfunction and mortality in murine inflammatory shock models. Am J Physiol Heart Circ Physiol 297:H654-63 |
| Yu, Binglan; Volpato, Gian Paolo; Chang, Keqin et al. (2009) Prevention of the pulmonary vasoconstrictor effects of HBOC-201 in awake lambs by continuously breathing nitric oxide. Anesthesiology 110:113-22 |
| Yu, Binglan; Bloch, Kenneth D; Zapol, Warren M (2009) Hemoglobin-based red blood cell substitutes and nitric oxide. Trends Cardiovasc Med 19:103-7 |
| Volpato, Gian Paolo; Searles, Robert; Yu, Binglan et al. (2008) Inhaled hydrogen sulfide: a rapidly reversible inhibitor of cardiac and metabolic function in the mouse. Anesthesiology 108:659-68 |
| Derumeaux, Genevieve; Ichinose, Fumito; Raher, Michael J et al. (2008) Myocardial alterations in senescent mice and effect of exercise training: a strain rate imaging study. Circ Cardiovasc Imaging 1:227-34 |
Showing the most recent 10 out of 104 publications
