There is growing evidence that cardiovascular disorders such as ischemic heart disease and hypertension may be related to a deficit in, or altered metabolism of, magnesium (Mg) in the cardiovascular system. These reports are supported by data showing that basal or stimulated tension development in a variety of isolated blood vessels is modified as the Mg concentration of physiological saline solution is altered. Most published studies of the interactions of Mg with Ca metabolism in vascular smooth muscle have utilized measurements of developed tension. Since tension development is the result of the interplay of multiple parameters including Ca influx, extrusion, and release, and membrane potential, the exclusive use of tension measurements cannot inambiguously identify specific sites at which Mg may act. The goal of the studies outlined in this proposal is to identify the specific sites at which Mg may regulate the plasmalemmal ion transport processes which in turn control tension development. The effect of alteration of solution Mg upon 1) tension development, 2) total cellular Ca, 3) 45Ca influx, 4) 45Ca efflux, and 5) membrane potential will be studied in quiescent arteries and those stimulated by norepinephrine or depolarizing media. These studies will be carried out in both aortae and mesenteric resistance vessels from normotensive and spontaneously hypertensive rats, in order to determine whether vascular smooth muscle cells in a widely used animal model of hypertension exhibit an abnormal sensitivity to Mg which might result in an increase in blood pressure. In addition, the effect of Mg upon passive fluxes of 86Rb and 22Na, and upon norepinephrine stimulated release of cellular Ca will be examined in aortae only. These experiments will seek to establish the Mg concentrations which exert maximal, and half-maximal, effects upon these parameters.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R23)
Project #
5R23HL032773-02
Application #
3448687
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-07-01
Project End
1987-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101