Abstract

The applicant raises the possibility that NO released from myocytes may be involved in the coronary vasodilation and enhanced myocardial diastolic relaxation observed with adrenergic induced increases in contractility. Accordingly, the applicant plans to test the hypothesis that cardiac myocytes contain a constitutive nitric oxide synthase (cNOS) under the regulation of norepinephrine and other possible endogenous mediators. The applicant will use a NO electrode to functionally characterize cardiac cNOS and pharmacologically dissect this pathway(s) involved in NO release.
The specific aims for the project are to definitively demonstrate and functionally characterize cardiac cNOS and to determine the mechanism(s) by which endogenous agonist evoke NO production by cardiac cNOS.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL057985-04
Application #
6056407
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1997-09-15
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2002-08-31
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Pharmacology
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Fike, Candice D; Kaplowitz, Mark R; Zhang, Yongmei et al. (2005) Cyclooxygenase-2 and an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs. J Appl Physiol 98:1111-8; discussion 1091
Kanai, Anthony; Epperly, Michael; Pearce, Linda et al. (2004) Differing roles of mitochondrial nitric oxide synthase in cardiomyocytes and urothelial cells. Am J Physiol Heart Circ Physiol 286:H13-21
Peterson, Jim; Kanai, Anthony J; Pearce, Linda L (2004) A mitochondrial role for catabolism of nitric oxide in cardiomyocytes not involving oxymyoglobin. Am J Physiol Heart Circ Physiol 286:H55-8
Fike, Candice D; Kaplowitz, Mark R; Pfister, Sandra L (2003) Arachidonic acid metabolites and an early stage of pulmonary hypertension in chronically hypoxic newborn pigs. Am J Physiol Lung Cell Mol Physiol 284:L316-23
Kanai, Anthony J; Zeidel, Mark L; Lavelle, John P et al. (2002) Manganese superoxide dismutase gene therapy protects against irradiation-induced cystitis. Am J Physiol Renal Physiol 283:F1304-12
Pearce, Linda L; Kanai, Anthony J; Birder, Lori A et al. (2002) The catabolic fate of nitric oxide: the nitric oxide oxidase and peroxynitrite reductase activities of cytochrome oxidase. J Biol Chem 277:13556-62
Birder, L A; Nakamura, Y; Kiss, S et al. (2002) Altered urinary bladder function in mice lacking the vanilloid receptor TRPV1. Nat Neurosci 5:856-60
Birder, Lori A; Nealen, Michele L; Kiss, Susanna et al. (2002) Beta-adrenoceptor agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci 22:8063-70