Our work on several models of hypertension in the rat has led us to conclude that the syndromes are associated not only with a pervasive change in arteriolar smooth muscle behavior, but also in the structural alignment of the various components of the microvascular network. Thus, both structural and functional adjustments are involved in chronic situations of this kind. Towards this end, we propose to combine intravital microscopy with detailed morphological studies to sort out functional as opposed to structural derrangements. Measurements include micropressure, velocity, flow and vessel tone distributions in a skeletal muscle (the spinotrapezius muscle of the rat) using two models of hypertension, the spontaneous, SHR form and that induced by high salt intake in a genetically predisposed strain, the Dahl rat. These animals will be examined longitudinally during their maturation and full expression of the hypertension and under the influence of pharmacologic agents used to bring systemic blood pressure to normal levels. Models of the microvascular network will be constructed from vessels injected and cleared whole mounts of muscle and histological characterization. These will be tested in the computer to determine the relative importance of the numerous variables involved. Such an approach should enable us to determine the effectiveness of given therapeutic regimes and to identify potentially new measures.
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