This application for a Mentored clinical Scientist Development Award is designed to provide the principal investigator (P.I.), Dr. Lynell Johnson, with the research skills and expertise needed to develop into an independent researcher in the field of cardiopulmonary research. Experience gained through completion of the research described will provide the P.I. with the skills needed to investigate more fully the physiology and molecular mechanisms involved in regulation of pulmonary vasoreactivity. With this knowledge, the P.I. can go beyond clinical studies of pulmonary diseases to engage in complementary scientific research. The P.I. is currently enrolled in a doctoral program with the Department of Veterinary Biomedical Sciences. Faculty members in this department are devoted to the study of cardiovascular disease and the benefits of exercise training on the vascular function, thus providing an excellent support system for the research described. The research planned will investigate the role of nitric oxide (NO) in enhancement of endothelium-dependent vasodilation in the pulmonary circulation using a porcine model of exercise training. Nitric oxide is recognized as an important endothelium-derived regulator of vascular responses in health individuals, and defects in NO-mediated responses are suspected in a number of pathophysiologic states. The central hypothesis of this research is that exercise training results in sustained adaptations in the pulmonary circulation through enhanced endothelium-mediated control of pulmonary vascular reactivity. The research proposed will utilize five methodologies encompassing basic physiology, biochemistry, and molecular biology, to test three hypotheses: 1) Increased blood flow associated with chronic exercise training leads to increased NO synthase and improved endothelium- mediated vasorelaxation in pulmonary arteries to exercise trained pigs, 2) Increased NO synthase induced by exercise training allows maintenance of lower vascular resistance at any give perfusion pressure in exercise trained subjects and reduces hypoxic pulmonary vasoconstriction, and 3) Increased blood flow through the lung leads to increased mRNA for nitric oxide synthase, thus providing a mechanism for improvement in endothelium-dependent vasorelaxation. The long term goal of this research is to gain the expertise needed for the P.I. to become an established investigator in cardiopulmonary research and to pursue independent funding for comparative studies on endothelium-mediated alterations in pulmonary vascular control in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003856-02
Application #
6030425
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (M2))
Project Start
1998-07-01
Project End
2002-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Johnson, Lynelle R; De Cock, Hilde E V; Sykes, Jane E et al. (2005) Cytokine gene transcription in feline nasal tissue with histologic evidence of inflammation. Am J Vet Res 66:996-1001
Johnson, Lynelle R; Foley, Janet E; De Cock, Hilde E V et al. (2005) Assessment of infectious organisms associated with chronic rhinosinusitis in cats. J Am Vet Med Assoc 227:579-85
Johnson, Lynelle R; Fry, Michael M; Anez, Kelly L et al. (2004) Histoplasmosis infection in two cats from California. J Am Anim Hosp Assoc 40:165-9
Windsor, Rebecca C; Johnson, Lynelle R; Herrgesell, Eric J et al. (2004) Idiopathic lymphoplasmacytic rhinitis in dogs: 37 cases (1997-2002). J Am Vet Med Assoc 224:1952-7
Johnson, Lynelle R; Drazenovich, Nicole L; Foley, Janet E (2004) A comparison of routine culture with polymerase chain reaction technology for the detection of Mycoplasma species in feline nasal samples. J Vet Diagn Invest 16:347-51
Johnson, Lynelle R; Clarke, Heather E; Bannasch, Michael J et al. (2004) Correlation of rhinoscopic signs of inflammation with histologic findings in nasal biopsy specimens of cats with or without upper respiratory tract disease. J Am Vet Med Assoc 225:395-400
Johnson, Lynelle R; Herrgesell, Eric J; Davidson, Autumn P et al. (2003) Clinical, clinicopathologic, and radiographic findings in dogs with coccidioidomycosis: 24 cases (1995-2000). J Am Vet Med Assoc 222:461-6
Johnson, L (2001) Small animal bronchoscopy. Vet Clin North Am Small Anim Pract 31:691-705, viii
Johnson, L R; Rush, J W; Turk, J R et al. (2001) Short-term exercise training increases ACh-induced relaxation and eNOS protein in porcine pulmonary arteries. J Appl Physiol 90:1102-10
Johnson, L R; Fales, W H (2001) Clinical and microbiologic findings in dogs with bronchoscopically diagnosed tracheal collapse: 37 cases (1990-1995). J Am Vet Med Assoc 219:1247-50

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