The long range goals of the studies described in this application are to elucidate how acute exposure to intermittent hypoxia-reoxygenation influences signaling mechanisms that control coronary and pulmonary vascular function. This laboratory has elucidated many aspects of how reactive oxygen species (ROS) and nitric oxide-derived species (RNS) interact with signaling systems which regulate processes that control vascular contraction and relaxation, and tissue respiratory processes, with an emphasis on how these mechanisms could function in responses elicited by changes in oxygen tension. It is hypothesized that ROS and RNS have important roles in the early modifications of vascular function caused by acute exposure to intermittent hypoxia. Thus, the overall goals of this project are to elucidate the roles of ROS and RNS in the initial alterations of vascular signaling mechanisms caused by exposure to intermittent hypoxia-reoxygenation that control the function of bovine coronary and pulmonary arteries.
The first aim focuses on determining how intermittent hypoxia-reoxygenation alters signaling mechanisms that control bovine coronary and pulmonary arterial smooth muscle contractile function.
The second aim examines how intermittent hypoxia-reoxygenation alters endothelium-derived signaling mechanisms that regulate coronary and pulmonary arterial function in large vessel and microvascular preparations.
The third aim studies how intermittent hypoxia-reoxygenation alters oxygen sensing signaling mechanisms that regulate coronary and pulmonary arterial function. These studies could provide fundamental information on how intermittent hypoxia contributes to the initial alterations in vascular function which could be important factors in the pathogenesis of vascular diseases associated with sleep apnea and related disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL066331-01
Application #
6233705
Study Section
Special Emphasis Panel (ZHL1-CSR-H (S1))
Project Start
2000-09-30
Project End
2004-08-31
Budget Start
2000-09-30
Budget End
2001-08-31
Support Year
1
Fiscal Year
2000
Total Cost
$273,875
Indirect Cost
Name
New York Medical College
Department
Physiology
Type
Schools of Medicine
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Alhawaj, Raed; Patel, Dhara; Kelly, Melissa R et al. (2015) Heme biosynthesis modulation via ?-aminolevulinic acid administration attenuates chronic hypoxia-induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 308:L719-28
Patel, Dhara; Alhawaj, Raed; Wolin, Michael S (2014) Exposure of mice to chronic hypoxia attenuates pulmonary arterial contractile responses to acute hypoxia by increases in extracellular hydrogen peroxide. Am J Physiol Regul Integr Comp Physiol 307:R426-33
Patel, Dhara; Kandhi, Sharath; Kelly, Melissa et al. (2014) Dehydroepiandrosterone promotes pulmonary artery relaxation by NADPH oxidation-elicited subunit dimerization of protein kinase G 1?. Am J Physiol Lung Cell Mol Physiol 306:L383-91
Neo, Boon Hwa; Patel, Dhara; Kandhi, Sharath et al. (2013) Roles for cytosolic NADPH redox in regulating pulmonary artery relaxation by thiol oxidation-elicited subunit dimerization of protein kinase G1?. Am J Physiol Heart Circ Physiol 305:H330-43
Chettimada, Sukrutha; Rawat, Dhwajbahadur K; Dey, Nupur et al. (2012) Glc-6-PD and PKG contribute to hypoxia-induced decrease in smooth muscle cell contractile phenotype proteins in pulmonary artery. Am J Physiol Lung Cell Mol Physiol 303:L64-74
Wolin, Michael S (2012) Novel role for the regulation of mitochondrial fission by hypoxia inducible factor-1? in the control of smooth muscle remodeling and progression of pulmonary hypertension. Circ Res 110:1395-7
Gupte, Sachin A; Wolin, Michael S (2012) Relationships between vascular oxygen sensing mechanisms and hypertensive disease processes. Hypertension 60:269-75
Neo, Boon Hwa; Kandhi, Sharath; Wolin, Michael S (2011) Roles for redox mechanisms controlling protein kinase G in pulmonary and coronary artery responses to hypoxia. Am J Physiol Heart Circ Physiol 301:H2295-304
Wolin, Michael S (2011) Plasma glutathione peroxidase activity is potentially a key regulator of vascular disease-associated thrombosis. Circulation 123:1923-4
Suematsu, Nobuhiro; Ojaimi, Caroline; Recchia, Fabio A et al. (2010) Potential mechanisms of low-sodium diet-induced cardiac disease: superoxide-NO in the heart. Circ Res 106:593-600

Showing the most recent 10 out of 63 publications