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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027020-08
Application #
3338876
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1982-04-01
Project End
1991-03-31
Budget Start
1989-04-01
Budget End
1991-03-31
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Kanagy, N L; Mecca, T E; Webb, R C (1996) Arachidonate metabolites and serotonin contraction of femoral arteries from DOCA-salt hypertensive rats. Blood Press 5:113-20
Watts, S W; Chai, S; Webb, R C (1995) Lead acetate-induced contraction in rabbit mesenteric artery: interaction with calcium and protein kinase C. Toxicology 99:55-65
Webb, R C; Schreur, K D; Papadopoulos, S M (1992) Oscillatory contractions in vertebral arteries from hypertensive subjects. Clin Physiol 12:69-77
Lee, L; Webb, R C (1992) Endothelium-dependent relaxation and L-arginine metabolism in genetic hypertension. Hypertension 19:435-41
Chai, S; Webb, R C (1992) Extracellular calcium, contractile activity and membrane potential in tail arteries from genetically hypertensive rats. J Hypertens 10:1137-43
Lee, L; Webb, R C; Pitt, B (1992) Eicosapentaenoic acid inhibits endothelium-dependent relaxation to acetylcholine in guinea pig coronary resistance vessels. Proc Soc Exp Biol Med 200:466-71
Turla, M B; Webb, R C (1991) Vascular responsiveness to protein kinase C activators in mineralocorticoid-hypertensive rats. J Hypertens 9:209-15
Weishaar, R E; Webb, R C; Smith, C B (1991) Changes in alpha 2-adrenoceptors on vascular smooth muscle and neural membranes following hypertension induced by renal ischemia. Pharmacology 43:187-98
Bohr, D F; Dominiczak, A F; Webb, R C (1991) Pathophysiology of the vasculature in hypertension. Hypertension 18:III69-75
Perry, P A; Webb, R C (1991) Agonist-sensitive calcium stores in arteries from steroid hypertensive rats. Hypertension 17:603-11

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