Abstract

The proposed research program will focus on properties of the cellular components of blood vessels, endothelium and smooth muscle, which influence their reactivity to vasoactive mediators. Using established, as well as newly developed methods, blood vessel cells (human, bovine, rodent) will be isolate and cultured for biochemical and physiological studies. Angiotensin II receptors will be characterized by radioligand binding assays, and the regulation and biochemical consequences of their activation studied, including interrelations with prostaglandin and cyclic nucleotide metabolism. Factors influencing endothelial cell angiotensin-I converting enzyme activity also will be studied. The above studies will be extended to vascular preparations obtained from spontaneously hypertensive rats and rats with experimentally-induced alterations in renin-angiotensin system activity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035013-04
Application #
3348482
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-01-01
Project End
1991-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Lassegue, B; Alexander, R W; Clark, M et al. (1993) Phosphatidylcholine is a major source of phosphatidic acid and diacylglycerol in angiotensin II-stimulated vascular smooth-muscle cells. Biochem J 292 ( Pt 2):509-17
Tsuda, T; Griendling, K K; Ollerenshaw, J D et al. (1993) Angiotensin-II-and endothelin-induced protein phosphorylation in cultured vascular smooth muscle cells. J Vasc Res 30:241-9
Griendling, K K; Taubman, M B; Akers, M et al. (1991) Characterization of phosphatidylinositol-specific phospholipase C from cultured vascular smooth muscle cells. J Biol Chem 266:15498-504
Lassegue, B; Alexander, R W; Clark, M et al. (1991) Angiotensin II-induced phosphatidylcholine hydrolysis in cultured vascular smooth-muscle cells. Regulation and localization. Biochem J 276 ( Pt 1):19-25
Socorro, L; Alexander, R W; Griendling, K K (1990) Cholera toxin modulation of angiotensin II-stimulated inositol phosphate production in cultured vascular smooth muscle cells. Biochem J 265:799-807
Tsuda, T; Alexander, R W (1990) Angiotensin II stimulates phosphorylation of nuclear lamins via a protein kinase C-dependent mechanism in cultured vascular smooth muscle cells. J Biol Chem 265:1165-70
Berk, B C; Vekshtein, V; Gordon, H M et al. (1989) Angiotensin II-stimulated protein synthesis in cultured vascular smooth muscle cells. Hypertension 13:305-14
Griendling, K K; Tsuda, T; Berk, B C et al. (1989) Angiotensin II stimulation of vascular smooth muscle. J Cardiovasc Pharmacol 14 Suppl 6:S27-33
Griendling, K K; Tsuda, T; Alexander, R W (1989) Endothelin stimulates diacylglycerol accumulation and activates protein kinase C in cultured vascular smooth muscle cells. J Biol Chem 264:8237-40
Berk, B C; Vallega, G; Muslin, A J et al. (1989) Spontaneously hypertensive rat vascular smooth muscle cells in culture exhibit increased growth and Na+/H+ exchange. J Clin Invest 83:822-9

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