Dr Ivy is a board certified pediatric cardiologist at the University of Colorado School of Medicine. He received his MD degree from Tulane University, and pediatrics and cardiology training from the Univ of CO SOM. As a Bugher Physician Scientist and Assistant Professor of Pediatrics, he has focused on clinical and basic science aspects of pulmonary hypertension in congenital heart disease and persistent pulmonary hypertension of the newborn. He has studied the role of endothelin (ET-1) in the normal fetal lung and in a model of pulmonary hypertension caused by in utero ligation of the ductus arteriosus. He has extensive experience in whole animal physiology, but only beginning training in molecular biology. RESEARCH: Pulmonary hypertension is a major cause of morbidity and mortality in children. ET-1 is a potent vasoconstrictor peptide which is increased in pulmonary hypertensive disorders; however, the role of ET-1 in pulmonary hypertension remains unclear. We will test the hypotheses that: 1) ET-1 acts in an autocrine fashion on vascular smooth muscle / ET-1 is produced on and stimulates smooth muscle proliferation 2) in chronic intrauterine pulmonary hypertension diminished nitric oxide production leads to elevated ET-1 production, 3) pressure stimulates production of ET-1 in the perinatal myocardium. The goals are: 1) to determine the cell specific expression of the ET system in the normal and hypertensive ovine fetal lung, 2) to determine if blockade of nitric oxide production leads to increased ET-1 production in the perinatal lung, 3) to determine the effect of changes in pressure on right and left ventricular expression of ET-1, ECE-1, and its receptors, and 4) to determine if blockade of endothelin converting enzyme activity attenuates chronic intrauterine pulmonary hypertension. ENVIRONMENT: Clinical and basic science studies of pulmonary hypertension are major focuses at the Univ of CO SOM. The laboratory environment at Univ of CO SOM comprises excellent clinicians / scientists with backgrounds in whole animal physiology and molecular techniques. Research presentations along with graduate level courses in molecular biology, and the clinical ambiance of the Univ of CO SOM in the area of pulmonary hypertension enhance career development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL003823-04
Application #
6526805
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (O1))
Program Officer
Colombini-Hatch, Sandra
Project Start
1999-09-15
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
4
Fiscal Year
2002
Total Cost
$128,250
Indirect Cost
Name
University of Colorado Denver
Department
Pediatrics
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Ivy, D Dunbar; McMurtry, Ivan F; Colvin, Kelley et al. (2005) Development of occlusive neointimal lesions in distal pulmonary arteries of endothelin B receptor-deficient rats: a new model of severe pulmonary arterial hypertension. Circulation 111:2988-96
Ivy, D Dunbar; Lee, Dong-Seok; Rairigh, Robyn L et al. (2004) Endothelin B receptor blockade attenuates pulmonary vasodilation in oxygen-ventilated fetal lambs. Biol Neonate 86:155-9
Drexler, E S; McCowan, C N; Wright, J E et al. (2004) Comparison of strength properties of normotensive and hypertensive rat pulmonary arteries. Biomed Sci Instrum 40:297-302
Carpenter, Todd; Schomberg, Stacey; Steudel, Wolfgang et al. (2003) Endothelin B receptor deficiency predisposes to pulmonary edema formation via increased lung vascular endothelial cell growth factor expression. Circ Res 93:456-63
Ivy, Dunbar; Tanzawa, Kazuhiko; Abman, Steven H (2002) Ontogeny of endothelin-converting enzyme gene expression and protein content in the ovine fetal lung. Biol Neonate 81:139-44
Ivy, D Dunbar; Yanagisawa, Masashi; Gariepy, Cheryl E et al. (2002) Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats. Am J Physiol Lung Cell Mol Physiol 282:L703-12
Ivy, D; McMurtry, I F; Yanagisawa, M et al. (2001) Endothelin B receptor deficiency potentiates ET-1 and hypoxic pulmonary vasoconstriction. Am J Physiol Lung Cell Mol Physiol 280:L1040-8
Ivy, D D; le Cras, T D; Parker, T A et al. (2000) Developmental changes in endothelin expression and activity in the ovine fetal lung. Am J Physiol Lung Cell Mol Physiol 278:L785-93
Ivy, D D; Parker, T A; Abman, S H (2000) Prolonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus. Am J Physiol Lung Cell Mol Physiol 279:L758-65
Ivy, D D; Le Cras, T D; Horan, M P et al. (1998) Increased lung preproET-1 and decreased ETB-receptor gene expression in fetal pulmonary hypertension. Am J Physiol 274:L535-41