The proposed research is based on the hypothesis that there is a sensitive period early in development when the physiological consequences of dietary NaCl can produce permanent effects on mechanisms involved in the control of sodium and blood pressure regulation. Studies are proposed to: (1) characterize further previously observed changes in NaCl exposure, and (2) determine whether these changes are also accompanied by changes in neuroendocrine mechanisms that control sodium and blood pressure regulation in normotensive Sprague-Dawley rats (S-DR), NaCl-sensitive spontaneously hypertensive rats (SHR-S), NaCl-resistant spontaneously hypertensive rats (SHR-R), and NaCl-resistant Wistar-Kyoto rats (WKY). A comparison of these four strains will provide a means for assessing the interaction between early NaCl exposure and genetic susceptibility to hypertension. Adult female rats will be fed diets that vary in NaCl content (0.12, 1, 3, 0r 8% NaCl) throughout pregnancy nad lactation. The offspring will be continued on the same NaCl diet until 30 days postpartum. Thereafter, all animals will be maintained on a control 1% NaCl diet and tested as adults. One goal is to determine whether early NaCl exposure alters NaCl intake during normal free-feeding conditions and after acute sodium deficiency induced by furosemide administration and 48 hours of dietary sodium deprivation. Altered taste mechanisms will be assessed by measuring changes in NaCl intake and electrophysiological responses of salt-sensitive taste neurons to NaCl stimulation after NaCl-taste receptor blockade with amiloride. To determine whether early NaCl exposure leads to primary hangs in excretion or intake, plasma and urinary electrolyte concentration, and plasma angiotensin II levels will be assessed in response to dietary NaCl deficiency and NaCl loading. A second goal is to determine whether early NaCl exposure leads to long-term changes in NaCl intake and blood pressure will be measured in response to intracranial infusions of All or an All- receptor antagonist in adult rats raised on either low, mid, or high NaCl diets. A third goal is to determine the window of sensitivity to early NaCl exposure. The effects of early dietary NaCl exposure, restricted to either prenatal, early postnatal (day 0-14), or early postweaning (day 15- 30) periods, on NaCl intake nad blood pressure of adult rats will be assessed. A final goal is to assess the effects of early dietary NaCl exposure on NaCl intake, electrolyte excretion, and blood pressure among SHR-S, SHR-R, and WKY.
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