Our previous work on several models of hypertension in the rat have led us to conclude that the chronically elevated phase of peripheral resistance is associated with both structural and functional adaptations in the microcirculation. The structural realignment involves all hierarchies of the arteriolar meshwork, the capillaries and the venules, but by itself can explain only in part the elevation of the microvascular resistance. Functional adjustments affect predominantly the tone in distributing arterioles and their side branches feeding the capillaries. After providing sufficient details of structural adjustments in the spinotrapezius muscle of spontaneously hypertensive rats, we propose to explore mechanisms underlying the elevated vascular tone. Under the challenge of a systemic elevation of blood pressure and the compensatory contraction of arteriolar vascular smooth muscle, a number of highly integrated microcirculatory functions are compromised, a situation that may contribute to the poor prognosis in hypertension; clearly documentation is needed. To meet these objectives, we propose to continue to combine intravital microscopy with modern quantitative morphological techniques. The influence of specific control mechanisms - myogenic, metabolic and neurogenic - on the microcirculation will constitute the main emphasis of our work. The influence of the elevated arteriolar tone, spontaneous vasomotor activity and blood cell distribution will be explored in hypertensives. Structural aspects of adrenergic innervation will be documented for the array of arterioles in muscle microcirculation. Measurements of micropressure, velocity, flow, diameter, tone, hematocrit, among others will be obtained in skeletal muscle of spontaneously hypertensive (SHR) and genetically predisposed salt dependent hypertensives (Dahl R and S strain). As an adjunct to our earlier studies of microcirculatory hemodynamics, our structural studies, and the development of models of the microcirculation, our program represents a concerted effort to identify the mechanisms for elevated vascular resistance and its consequence on tissue homeostasis. This type of approach should enable us to evaluate the effectiveness of current therapeutic interventions and to identify potentially new departures.
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