Abstract

Portal hypertension (PHT) and its complications account for over 100,000 deaths in the United States, making it one of the top four causes of death. Due to our lack of understanding of the etiology of the altered vasoregulation in PHT, treatment has not been directed at reversing these abnormalities. This proposal will determine the receptor and G-protein- linked signal mechanism alterations mediated by nitric oxide and prostacyclin, the two peptide hormones judged most responsible for the vascular hyperemia of PHT. The relationship between increased shear stress and/or pressure and the altered vasoregulation in PHT will also be assessed. A rat model of PHT will be used, together with vascular smooth muscle cells (VSMC) in static culture and co-cultures of VSMG, and endothelial cells exposed to variable shear stress and/or pressure. These experiments should provide valuable information central to our understanding of PHT and vasoregulation in other vascular hypertensive events.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32DK009223-01
Application #
2136265
Study Section
Surgery and Bioengineering Study Section (SB)
Program Officer
Hyde, James F
Project Start
1995-09-05
Project End
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
Georgetown University
Department
Surgery
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057

  Publications

Redmond, E M; Cullen, J P; Cahill, P A et al. (2001) Endothelial cells inhibit flow-induced smooth muscle cell migration: role of plasminogen activator inhibitor-1. Circulation 103:597-603
Redmond, E M; Cahill, P A; Hirsch, M et al. (1999) Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase. Thromb Haemost 81:293-300
Hendrickson, R J; Okada, S S; Cahill, P A et al. (1999) Ethanol inhibits basal and flow-induced vascular smooth muscle cell migration in vitro. J Surg Res 84:64-70
Hendrickson, R J; Cappadona, C; Yankah, E N et al. (1999) Sustained pulsatile flow regulates endothelial nitric oxide synthase and cyclooxygenase expression in co-cultured vascular endothelial and smooth muscle cells. J Mol Cell Cardiol 31:619-29
Hendrickson, R J; Cahill, P A; Sitzmann, J V et al. (1999) Ethanol enhances basal and flow-stimulated nitric oxide synthase activity in vitro by activating an inhibitory guanine nucleotide binding protein. J Pharmacol Exp Ther 289:1293-300
Cappadona, C; Redmond, E M; Theodorakis, N G et al. (1999) Phenotype dictates the growth response of vascular smooth muscle cells to pulse pressure in vitro. Exp Cell Res 250:174-86
Redmond, E M; Cahill, P A; Sitzmann, J V (1998) Flow-mediated regulation of G-protein expression in cocultured vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol 18:75-83
Hendrickson, R J; Cahill, P A; McKillop, I H et al. (1998) Ethanol inhibits mitogen activated protein kinase activity and growth of vascular smooth muscle cells in vitro. Eur J Pharmacol 362:251-9
Redmond, E M; Cahill, P A; Sitzmann, J V (1997) Flow-mediated regulation of endothelin receptors in cocultured vascular smooth muscle cells: an endothelium-dependent effect. J Vasc Res 34:425-35