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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037753-06
Application #
3353730
Study Section
Special Emphasis Panel (SRC)
Project Start
1987-07-01
Project End
1992-09-29
Budget Start
1990-09-30
Budget End
1992-09-29
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost
Name
West Virginia University
Department
Type
Schools of Medicine
DUNS #
191510239
City
Morgantown
State
WV
Country
United States
Zip Code
26506
Johnson, M D; Zhang, H Y; Kotchen, T A (1993) Sucrose does not raise blood pressure in rats maintained on a low salt intake. Hypertension 21:779-85
Dubey, R K; Zhang, H Y; Reddy, S R et al. (1993) Pioglitazone attenuates hypertension and inhibits growth of renal arteriolar smooth muscle in rats. Am J Physiol 265:R726-32
Reddy, S R; Kotchen, T A (1992) Hemodynamic effects of high dietary intakes of sodium or chloride in the Dahl salt-sensitive rat. J Lab Clin Med 120:476-82
Reddy, S R; Kotchen, T A (1992) Dietary sodium chloride increases blood pressure in obese Zucker rats. Hypertension 20:389-93
Boegehold, M A; Kotchen, T A (1991) Importance of dietary chloride for salt sensitivity of blood pressure. Hypertension 17:I158-61
Kotchen, T A; Kotchen, J M; Boegehold, M A (1991) Nutrition and hypertension prevention. Hypertension 18:I115-20
Kong, J Q; Curto, K A; Fleming, W W et al. (1991) Catecholamine and neuropeptide Y levels in tissues from young Dahl rats following 5 days low- or high-salt diet. Blood Vessels 28:442-51
Kong, J Q; Taylor, D A; Fleming, W W et al. (1991) Specific supersensitivity of the mesenteric vascular bed of Dahl salt-sensitive rats. Hypertension 17:349-56
Reddy, R S; Baylis, C; Kotchen, T A (1991) Hemodynamic responses to acute volume expansion in Dahl salt-sensitive rats. Am J Physiol 260:R32-8
Kotchen, T A; Blehschmidt, N G; Reddy, S R (1991) Effect of dietary NaCl on norepinephrine turnover in the Dahl rat. J Lab Clin Med 117:383-9

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