Morphological changes occur in microvessels during development of hypertension. Thickening of arteriolar walls and alterations in actual number of certain vessels have been reported in hypertensive animals and humans. Sensitivity to humoral agents also may be increased. The implication of these changes for capillary fluid exchange, regulation of blood flow, and development and maintenance of hypertension are just beginning to be explored. We propose to use direct microcirculatory techniques on gracilis muscle and mesenteric vascular beds, including: in vivo quantitative stereology using intravital fluoromicroscopy for vessel length and surface area densities, television microscopy for vessel diameters and wall/lumen ratios, red cell velocity by the dual-slit photometric method, servo-null micropressures, and application of vasoactive agents with micropipettes, to investigate microcirculatory dynamics during development of hypertension in several rat models. Longitudinal studies of the microvascular alterations will be made in SHR, 1-kidney-1-clip, 1-kidney-1-clip, DOCA-salt, and Dahl hypertensive rats. To determine the relative influence of neural, and local/humoral mechanisms, measurements will be made in 3 consecutive states, innervated, denervated, and vasodilated. Comparison of the 5 models will implicate mechanisms responsible for the structural changes as well as determine whether structural alterations are specific to a certain type of hypertension, or commonly shared. Microvascular pressure profiles and red cell velocity data will add physiological information to correlate with observed morphological alterations. Various antihypertensive agents will be used chronically and acutely to determine the mechanisms leading to the microvascular alterations. Sensitivity to norepinephrine, angiotensinII and vasopressin will be determined by direct application to the microvessels with micropipettes. The functional significance of microvascular alterations will be investigated by studying exercise hyperemia, reactive hyperemia, and myogenic responses of microvessels in these hypertensive models. These studies will provide information to assess structural alterations in the microcirculation and to determine their cause, role, and functional significance in hypertension.
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