The existence and the possible role of a Na+ Ca2+ exchange process in the cell membrane of vascular smooth muscle is far from established. Studies with intact tissues on the existence of a Na+ Ca2+ exchange process have resulted in conflicting reports. An alternative approach to this problem is to isolate sarcolemmal membranes from vascular smooth muscle and to study the Na+ Ca2+ exchange process in vitro eliminating interference by other membranes and ion transport processes. Preliminary studies indicate that a Na+ Ca2+ exchange process does, in fact, exist in isolated sarcolemmal membranes of rat mesenteric arteries.
The aim of the proposed research is to determine the presence of a similar Na+ Ca2+ exchange process in other vascular smooth muscles, its monovalent and divalent cation specificity, its stoichiometry, its kinetic characteristics, its regulation, and possible role. These studies will be carried out with sarcolemmal membrane vesicles isolated from a variety of vascular smooth muscles. These studies should lead to a better understanding of the role of Na+ Ca2+ exchange in the Ca2+ homeostasis of the vascular smooth muscle cells. The information obtained from the proposed study may explain conflicting reports and may also help in designing rational experiments to determine its role in cell functions. Since Na+ is linked to several forms of hypertension, a Na+ Ca2+ exchange process may play a role in the maintenance of higher intracellular Ca2+ and increased steady state tension of resistant arteries which may contribute to the development and/or maintenance of hypertension. Thus, the Na+ Ca2+ exchange process of vascular smooth muscle may become one of the targets for pharmacological interventions to control hypertension.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL034664-03
Application #
3347810
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1985-08-01
Project End
1988-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
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Matlib, M A (1988) Na+-Ca2+ exchange in sarcolemmal membrane vesicles of dog mesenteric artery. Am J Physiol 255:C323-30
French, J F; Matlib, M A (1988) Identification of a high-affinity peripheral-type benzodiazepine binding site in rat aortic smooth muscle membranes. J Pharmacol Exp Ther 247:23-8
Matlib, M A; Kihara, M; Farrell, C et al. (1988) The Na+-Ca2+ exchange system in vascular smooth muscle cell membrane vesicles isolated from cultured cells and from tissue is similar. Biochim Biophys Acta 939:173-7

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