A significant fraction of the human population with essential hypertension is salt-sensitive, i.e., high NaCl intake further increases blood pressure. The Dahl rat is selectively bred to be either susceptible (Dahl-S) or resistant (Dahl-R) to the hypertensive effects of increased dietary NaCl. The Dahl-S rat, a model of human salt-sensitive hypertension, develops hypertension primarily through an increase in peripheral vascular resistance. However, the microvascular alterations responsible for this resistance increase are unknown. This study has four main goals; (1) To identify any inherent microvascular differences between the Dahl-R and Dahl-S strains which are unrelated to high NaC1 intake, (2) to determine the functional changes in the microvasculature which contribute to the onset of NaCl-induced hypertension in the Dahl-S rate, (3) to identify structural and functional changes in the microvasculature which increase peripheral resistance in moderate and severe NaCl-induced hypertension and (4) to assess the neurogenic contribution to the microvascular alterations associated with moderate and severe NaCl-induced hypertension. Before and at various stages after initiation of a high (7%) NaCl diet, the arteriolar network in Dahl-S intestine and skeletal muscle will be examined by intravital microscopy. Alterations related to increased vascular tone (density of perfused arterioles and their diameters) and structural reorganization of the network (anatomical arteriolar density) will be investigated. At each developmental stage, whole-organ resistance will also be calculated from microsphere-determined blood flow measurements, and microvascular pressures will be measured to determine the fractional distribution of resistance across the vascular bed. This information will permit the hemodynamic effect of each identifiable microvascular alteration to be quantified. The influence of sympathetic neural activity on the arteriolar network will be evaluated by determining the effect of local neural blockade on the number of perfused arterioles and their diameters. Microvascular responsiveness to norepinephrine will also be assessed by its iontophoretic application to individual arterioles. To distinguish between those characteristics related specifically to high NaCl intake in the Dahl-S rat and those related to either diet or strain alone, all of the above measurements will be made as well in three separate control groups: Dahl-S on a 0.45% NaCl diet and Dahl-R on both 7% and 0.45% NaCl diets.
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