The overall objective is to evalute the mechanism(s) by which NaCl produces hypertension in an experimental model of salt sensitive hypertension (Dahl-S rat) and in man. We hypothesize that salt sensitivity is related to an expanded ECF volume, increased sympathetic tone, and/or decreased baroreflex sensitivity. Because mechanisms involved in the initiation and maintenance of hypertension may differ, pre-hypertensive"""""""" and hypertensive rats and man will be studied. In the Dahl-S rat, hypertension depends on high dietary intakes of both sodium and chloride. We will study Dahl-S and Dahl salt resistant rats (R) on """"""""normal"""""""" NaCl, high NACl, high sodium-""""""""normal"""""""" chloride, or """"""""normal"""""""" sodium-high chloride diets. In man, we are following a cohort of young adults to evaluate the hypothesis that individuals with relatively high blood pressure are at increased risk for developing hypertension. This population provides the unique opportunity to study salt sensitivity in """"""""pre-hypertensive"""""""" man. Salt sensitivity will be defined by the reduction of blood pressure in response to NaCl deprivation. Studies will be carried out in normotensive, """"""""pre-hypertensive"""""""", and hypertensive subjects on high and again on low NaCl intakes. In the rat and man, we will measure cardiac output, ECF volume, and plasma volume. Sympathetic tone will be assessed by basal and stimulated plasma catecholamines (rat and man), tissue norepinephrine turnover (rat), effect of ganglionic blockade on vascular resistance (rat), norepinephrine spillover and clearance (man), and effects of tilt and isometric exercise on blood pressure, heart rate, and peripheral resistance (man). To evaluate arterial baroreflex sensitivity, heart rate responses (rat and man) and direct recordings of sympathetic nerve activity (rat) to infusions of phenylephrine and nitroprusside will be studied. Cardiopulmonary baroreflex sensitivity (effect of lower body negative pressure on heart rate, peripheral resistance) will be studied in man. In the rat, we hypothesize that: 1) NaCl loading will have a greater effect on ECF volume and neural activity in the Dahl-S than in the Dahl-R rat, and 2) selective sodium or selective chloride loading in the Dahl-S rat will neither increase ECF nor affect neural activity. In man, in comparison to salt insensitive subjects, we hypothesize that salt sensitive individuals will have: 1) a greater reduction of ECF volume in response to NaCl deprivation, and 2) increased sympathetic tone and decreased baroreflex sensitivity on a high NaCl diet.
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