HIGH SALT DIET, ANGIOTENSIN II, AND MICROVESSEL DILATION

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DESCRIPTION (Adapted from the applicant's abstract): Diets with high salt content are common in Western society, and have long been implicated as a risk factor for hypertension. Historically, it has been believed that the high salt diet leads to an elevated blood pressure in salt sensitive individuals, and that this elevation in arterial pressure leads to pathological alterations in vessel function. However, recent studies suggest that elevated salt intake also affects vessel structure and reactivity in normotensive animals, and that these alterations are mediated via angiotensin II (ANG II) suppression. These novel and important observations have substantial clinical implications, since they demonstrate that the impaired vasodilator responses reported in many forms of salt sensitive hypertension may not depend on the elevation of blood pressure. This raises the possibility that, when combined with other predisposing factors, altered vascular reactivity with elevated salt intake could lead to the development of salt sensitive hypertension. This project will utilize isolated, cannulated resistance arteries and in situ microcirculatory preparations to test the central hypothesis that elevated salt intake per se leads to impaired vasodilator reactivity in arterioles and resistance arteries of normotensive animals, and that this effect is mediated via suppression of ANG II. The specific aims of this study are: 1) to determine whether the impaired vascular relaxation occurring in response to high salt diet is due to alterations in the vascular smooth muscle cells, alterations in endothelial function, or both; 2) to evaluate the role of electrophysiological mechanisms in contributing to the impaired response to vasodilator stimuli in animals on a high salt diet; 3) to determine the role of ANG II and specific ANG II receptor subtypes in maintaining normal vasodilator responses in animals on a high salt diet. Elucidating the mechanism of the altered vascular reactivity that occurs in arterioles and resistance arteries of animals on a high salt diet can lead to an increased understanding of this novel role of ANG II in regulating vasodilator responses in the absence of the confounding effects of elevated arterial pressure.