Abstract

We will investigate the hypothesis that a) microcirculatory exchange function is regulated by a system of checks and balances, and b) biochemical and molecular interactions between agonists and endothelium play a role in controlling microcirculatory exchange function. This hypothesis will be approached by pursuing the following aims: 1) to determine and characterize the differential resistance and exchange vessel responses to bradykinin (BK), adenosine (ADO) and platelet activating factor (PAF); 2) to determine the influence of leukocyte adhesion and migration on macromolecular transport; and 3) to determine the biochemical pathways by which ADO, BK and PAF influence microcirculatory exchange function. Intravital fluorescent videomicroscopy, spectrofluorometry, radioimmunoassay and computer assisted videoimage digital processing methods will be used to measure transport of macromolecules in the hamster cheek pouch microcirculation. Inhibitors of calcium entry (verapamil) and of protein kinase C (sphingosine) will be applied to gain insight into the molecular events produced by the interactions between agonists and endothelium. It is submitted that the results of this project will provide an important key to the understanding of the regulatory mechanisms of microcirculatory exchange. This knowledge of microcirculatory pathophysiology is essential for the development of therapy for inflammation and vascular diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL043146-03
Application #
3361627
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1991-01-01
Project End
1995-12-31
Budget Start
1993-01-01
Budget End
1993-12-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of Medicine & Dentistry of NJ
Department
Type
Schools of Medicine
DUNS #
605799469
City
Newark
State
NJ
Country
United States
Zip Code
07107

  Publications

Varma, Shubha; Breslin, Jerome W; Lal, Brajesh K et al. (2002) p42/44MAPK regulates baseline permeability and cGMP-induced hyperpermeability in endothelial cells. Microvasc Res 63:172-8
Lal, B K; Varma, S; Pappas, P J et al. (2001) VEGF increases permeability of the endothelial cell monolayer by activation of PKB/akt, endothelial nitric-oxide synthase, and MAP kinase pathways. Microvasc Res 62:252-62
Kim, D D; Ramirez, M M; Duran, W N (2000) Platelet-activating factor modulates microvascular dynamics through phospholipase C in the hamster cheek pouch. Microvasc Res 59:13-Jul
Duran, W N; Seyama, A; Yoshimura, K et al. (2000) Stimulation of NO production and of eNOS phosphorylation in the microcirculation in vivo. Microvasc Res 60:104-11
Pappas, P J; You, R; Rameshwar, P et al. (1999) Dermal tissue fibrosis in patients with chronic venous insufficiency is associated with increased transforming growth factor-beta1 gene expression and protein production. J Vasc Surg 30:1129-45
Duran, W N; Takenaka, H; Hobson 2nd, R W (1998) Microvascular pathophysiology of skeletal muscle ischemia-reperfusion. Semin Vasc Surg 11:203-14
Takenaka, H; Oshiro, H; Kim, D D et al. (1998) Microvascular transport is associated with TNF plasma levels and protein synthesis in postischemic muscle. Am J Physiol 274:H1914-9
Kim, D; Duran, W T; Daniels, A J et al. (1997) Novel neuropeptide Y receptor antagonists block vasoconstriction in the hamster cheek pouch microcirculation. Microvasc Res 53:167-72
Milazzo, V J; Ferrante, R J; Sabido, F et al. (1996) Time course of leukocyte adhesion to endothelium in ischemia-reperfusion. J Surg Res 61:139-42
Duran, W N; Milazzo, V J; Sabido, F et al. (1996) Platelet-activating factor modulates leukocyte adhesion to endothelium in ischemia-reperfusion. Microvasc Res 51:108-115

Showing the most recent 10 out of 32 publications