Current knowledge about hypertension suggests that an elevated peripheral resistance maintains high levels of arterial pressure. This increase in peripheral resistance may be caused by a vasoconstriction resulting from an alteration in vascular smooth muscle which makes it more sensitive to normal stimuli. There is evidence that this increased sensitivity reflects a primary change in the membrane of vascular smooth muscle cells. The long-term objective of this research is to develop a more complete understanding of functional vascular changes in hypertension. Experiments proposed in this research plan will test the following hypotheses: 1) augmented vascular sensitivity in hypertensive animals is due to a decreased ability of calcium ions to stabilize membrane properties; 2) membrane bound calcium that serves as a source of activator calcium is decreased in vascular smooth muscle of hypertensive animals; 3) sodium intake will influence vascular reactivity in a genetically hypertensiverat strain; and 4) altered vascular reactivity (reduced calcium stabilization, electrogenic pump inhibition, norepinephrine-induced phasic contractions) is genetically linked to elevated blood pressure. The proposed experiments will be performed on isolated blood vessel segments (aorta, mesenteric artery, tail artery) from hypertensive and normotensive rats. The techniques used to evaluate vascular function include: 1) isometric recording of contractile behavior; 2) biochemical assay procedures (calcium binding in membrane fractions; calcium flux measurements in intact tissue); and 3) analyses of vascular traits in a genetic experiment. It is anticipated that this study will yield important information about functional determinants of vascular reactivity in hypertension.
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