This project will investigate the several MACRO and MICROCIRCULATORY factors which act in concert to produce the elevated peripheral resistance seen in hypertension. It is our general hypothesis that there are MULTIPLE HEMODYNAMIC PATHWAYS to established hypertension, with the particular hemodynamic pattern individualized because of different cardiovascular reactivities. Our specific hypothesis is that different systemic and microvascular reactivities to environmental stressors and stimuli produce distinctive hemodynamic responses, which then cause more long-term vascular structural alterations. We also propose that these structural changes are brought about principally by factors involved in long-term autoregulation or local control of blood flow. Functional and structural alterations of the vasculature in hypertension have been extensively documented, in terms of internal diameter, wall thickness, total number of parallel arterioles and percentage of open vessels. Our approach to these hypotheses involves investigating systemic and microvascular reactivity in unanesthetized animals, determining the pathophysiological interaction of simultaneously applied vasoactive agents, research the local and neural factors controlling vascularity, and correlating these studies with findings in human essential hypertensives. The experimental models will be skeletal muscle and brain vasculature of the Dahl salt-sensitive rat (Dr. John Rapp strain), the Spontaneously Hypertensive Rat (SHR), and the chick chorioallantoic membrane (CAM).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL013936-13
Application #
3334704
Study Section
Cardiovascular and Pulmonary Research B Study Section (CVB)
Project Start
1979-04-01
Project End
1990-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Type
Schools of Medicine
DUNS #
041418799
City
Winston-Salem
State
NC
Country
United States
Zip Code
27106
Hutchins, P M; Lynch, C D; Cooney, P T et al. (1996) The microcirculation in experimental hypertension and aging. Cardiovasc Res 32:772-80
Dusseau, J; Hutchins, P M (1993) Calcium entry blockers stimulate vasoproliferation on the chick chorioallantoic membrane. Int J Microcirc Clin Exp 13:219-31
Yuan, X Q; Smith, T L; Prough, D S et al. (1990) Long-term effects of nimodipine on pial microvasculature and systemic circulation in conscious rats. Am J Physiol 258:H1395-401
Lefer, D J; Lynch, C D; Lapinski, K C et al. (1990) Enhanced vasomotion of cerebral arterioles in spontaneously hypertensive rats. Microvasc Res 39:129-39
Lynch, C; Roddick, V; Hutchins, P (1989) Altered microvascular response to adenosine in the spontaneously hypertensive rat. Microvasc Res 38:164-74
Dusseau, J W; Hutchins, P M (1989) Microvascular responses to chronic hypoxia by the chick chorioallantoic membrane: a morphometric analysis. Microvasc Res 37:138-47
Dusseau, J W; Hutchins, P M (1988) Hypoxia-induced angiogenesis in chick chorioallantoic membranes: a role for adenosine. Respir Physiol 71:33-44
Hutchins, P M; Marshburn, T H; Smith, T L et al. (1988) Correlation of macro and micro cardiovascular function during weightlessness and simulated weightlessness. Acta Astronaut 17:253-6
Khraibi, A A; Smith, T L; Hutchins, P M et al. (1987) Thymectomy delays the development of hypertension in Okamoto spontaneously hypertensive rats. J Hypertens 5:537-41
Dusseau, J W; Hutchins, P M; Malbasa, D S (1986) Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane. Circ Res 59:163-70

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