NEURAL CONTROL OF RENAL FUNCTION IN HYPERTENSION

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The proposed research is designed to examine the physiological and pathophysiological significance of the neural control of renal function in hypertension. How the interaction of environmental and genetic factors, activity of the sympathetic nervous system, and alterations in renal function contribute to the development, maintenance, and exacerbation of hypertension will be investigated in two main ways: 1) examining mechanisms of the acute effects of environmental stress on arterial pressure control mechanisms (brain, kidneys) in conscious hypertensive rat models; and 2) examining the importance of these mechanisms in the pathogenesis of hypertension resulting from exposure to chronic environmental stress. In these studies, environmental stress will be used as a physiological stimulus to activate sympathetic outflow in conscious rats. Specific Aim #1 will determine whether alpha- or beta-adrenoceptors in the central amygdaloid nucleus mediate the increased renal sympathetic nerve activity and antinatriuresis resulting from acute exposure to environmental stress (air stress) in conscious spontaneously hypertensive rats. Specific Aim #2 will examine whether the enhanced renal sympathetic nerve activity and antinatriuretic responses to air stress in spontaneously hypertensive rats on high sodium intake are mediated via central nervous system alpha-2 adrenoceptors. Whether the renal vasculature and tubules of spontaneously hypertensive rats on high sodium intake are more sensitive to increases in renal sympathetic nerve activity than spontaneously hypertensive rats on normal sodium intake will also be examined. Specific Aim #3 addresses the question of whether environmental stress increases renal sympathetic nerve activity and decreases urinary sodium excretion in other conscious hypertensive rat models, i.e., DOCA-salt, Dahl salt-sensitive, and borderline (crossbred SHR x WKY) hypertensive rats. Specific Aim #4 will examine whether chronic exposure to environmental stress produces or exacerbates hypertension in conscious rats by increasing renal sympathetic nerve activity, thus enhancing renal sodium retention. Specific Aim #5 will examine whether high sodium diet accelerates the development or progression of hypertension resulting from chronic exposure to environmental stress by further enhancing renal sympathetic nerve activity and renal sodium retention.