The concentration of Na inside vascular smooth muscle cells in an important regulator of vascular smooth muscle function, however little is known about the sarcolemmal translocation pathways which mediate Na influx. Prior studies have shown that Na flux into arterial strips is increased in several forms of experimental hypertension, but the translocation pathways involved are not known. These studies will test the hypotheses that specific transport mechanisms which mediate Na influx are present in the sarcolemma of of vascular smooth muscle cells, that an increase in the activity of one or more of these transport systems is found in mineralocorticoid induced hypertension, and that this effect of mineralocorticoids is mediated via methylation of membrane components. It is proposed to test for the presence of, and characterize four specific Na translocation pathways in sarcolemmal vesicles from canine superior mesenteric artery: 1) Na channels; 2) Na/H exchange; 3) Na/K/Cl cotransport; 4) Na/Ca exchange. The effects of aldosterone in-vitro, and DOCA-salt hypertension on the activities of these pathways will be determined. Finally, the relation between aldosterone-stimulated Na transport and the methylation of sarcolemmal phospholipids and proteins will be assessed. These studies will contribute to the fundamental understanding of Na metabolism in vascular smooth muscle cells, under normal and abnormal conditions. Such information may help establish the pathogenesis of certain hypertensive states, and lead to the development of specific therapies for these diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL040480-05
Application #
3471976
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1988-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1994-07-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Kahn, A M; Lichtenberg, R A; Allen, J C et al. (1995) Insulin-stimulated glucose transport inhibits Ca2+ influx and contraction in vascular smooth muscle. Circulation 92:1597-603
Kahn, A M; Allen, J C; Seidel, C L et al. (1994) Insulin inhibits serotonin-induced Ca2+ influx in vascular smooth muscle. Circulation 90:384-90
Kahn, A M; Seidel, C L; Allen, J C et al. (1993) Insulin reduces contraction and intracellular calcium concentration in vascular smooth muscle. Hypertension 22:735-42
Kahn, A M; Bishara, M; Cragoe Jr, E J et al. (1992) Effects of serotonin on intracellular pH and contraction in vascular smooth muscle. Circ Res 71:1294-304
Halligan, R D; Shelat, H; Kahn, A M (1991) Na(+)-independent Cl(-)-HCO3- exchange in sarcolemmal vesicles from vascular smooth muscle. Am J Physiol 260:C347-54
Kahn, A M; Cragoe Jr, E J; Allen, J C et al. (1991) Effects of pHi on Na(+)-H+, Na(+)-dependent, and Na(+)-independent C1(-)-HCO3-exchangers in vascular smooth muscle. Am J Physiol 261:C837-44
Kahn, A M; Cragoe Jr, E J; Allen, J C et al. (1990) Na(+)-H+ and Na(+)-dependent Cl(-)-HCO3- exchange control pHi in vascular smooth muscle. Am J Physiol 259:C134-43