This proposal will examine the effects of various vasoactive agents (alpha1 and alpha2 adrenergic, angiotensin, serotonin, beta adrenergic and other compounds that alter cyclic AMP) on the activity of the Na/K pump in canine vascular smooth muscle. Specifically, studies will determine whether these agents activate the pump indirectly by increasing ion availability and/or directly by modifying pump function. To examine these possibilities, the investigator will employ a variety of experimental approaches and preparations. Studies on intact tissues will examine the effects of agonists on pump function, Na contents and cyclic AMP levels. Studies on membrane fractions will investigate cyclic AMP dependent changes in Na/H or Na/Ca exchange that could secondarily affect Na/K pump activity. Molecular biological approaches will examine mRNAs for the a and b subunits of the Na/K pump and define their content and will use PCR to produce a cDNA probe for screening vascular smooth muscle (VSM) libraries to identify the two mRNAs that appear to code for the a subunit and other possible subunit isoforms.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL024585-13
Application #
2215775
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1980-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
13
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Zhang, Sui; Yang, Yu; Kone, Bruce C et al. (2003) Insulin-stimulated cyclic guanosine monophosphate inhibits vascular smooth muscle cell migration by inhibiting Ca/calmodulin-dependent protein kinase II. Circulation 107:1539-44
Kahn, Andrew M; Allen, Julius C; Zhang, Sui (2002) Insulin increases NADH/NAD+ redox state, which stimulates guanylate cyclase in vascular smooth muscle. Am J Hypertens 15:273-9
Aydemir-Koksoy, A; Abramowitz, J; Allen, J C (2001) Ouabain-induced signaling and vascular smooth muscle cell proliferation. J Biol Chem 276:46605-11
Aydemir-Koksoy, A; Allen, J C (2001) Regulation of Na(+) pump expression by vascular smooth muscle cells. Am J Physiol Heart Circ Physiol 280:H1869-74
Aydemir-Koksoy, A; Allen, J C (2001) Low concentrations of ouabain induce vascular smooth muscle cell proliferation. Cell Mol Biol (Noisy-le-grand) 47:341-5
Abramowitz, J; Aydemir-Koksoy, A; Helgason, T et al. (2000) Expression of plasma membrane calcium ATPases in phenotypically distinct canine vascular smooth muscle cells. J Mol Cell Cardiol 32:777-89
Kahn, A M; Allen, J C; Seidel, C L et al. (2000) Insulin increases NO-stimulated guanylate cyclase activity in cultured VSMC while raising redox potential. Am J Physiol Endocrinol Metab 278:E627-33
Burns, A R; Bowden, R A; MacDonell, S D et al. (2000) Analysis of tight junctions during neutrophil transendothelial migration. J Cell Sci 113 ( Pt 1):45-57
Kahn, A M; Allen, J C; Seidel, C L et al. (2000) Insulin inhibits migration of vascular smooth muscle cells with inducible nitric oxide synthase. Hypertension 35:303-6
Kahn, A M; Allen, J C; Seidel, C L et al. (2000) Protein kinase C mediates insulin-inhibited Ca2+ transport and contraction of vascular smooth muscle. Am J Hypertens 13:383-8

Showing the most recent 10 out of 27 publications