Abstract

The main hypothesis of this proposal is that the central nervous system contributes to the increased hypertension when high sodium chloride diets are given. The effect is considered to be due to a decrease in norepinephrine (NE) release from terminals in the anterior hypothalamic area (AHA). The concept is that a decrease of noradrenergic (NA) release in the anterior hypothalamus (AH) earlier mediates a decrease in sympathoinhibition and consequently blood pressure rises. To test this a rat model will be used which is sensitive to the effects of sodium chloride and is spontaneously hypertensive. This is the SHR-S rat. As controls, the SHR-resistant rat and the normotensive WKY rat will be used.
The first aim i s to test the hypothesis that a decrease in NE release from the AH of SHR-S precedes the development of NaCl-exacerbated hypertension. In a separate experiment NE will be infused chronically into the AHA of rats on a high NaCl diet in an attempt to prevent the appearance of the exacerbated hypertension. The mechanism of the decrease in NE in the AH is hypothesized to be due to a change in baroreflex neurons providing NE to the AHA area or inhibition of any release by neurotransmitters within the AHA. To test this, microdialysis and/or push-pull techniques will be used to provide data for the hypothesis that endogenous atrial natriuretic peptide (ANP) regulates NE release in the AH and secondly, that this peptide is regulated in the SHR-S rat by the NaCl diet.
In specific aim 2 the goal of the baroreflex in the NE decrease will be studied. This involves electrophysiological mapping of the AHA neurons which respond to baroreceptor activation.
In specific aim 3 the anatomical connections of the AHA which are involved in sympathoinhibitory function will be defined. An attempt will be made to determine whether specific changes of NE axons in the AHA area occur in the SHR-S rat and the percentage of neurons containing NE which send collaterals to the AHA will be measured. With these studies the investigator hopes to determine the mechanism of increased hypertension with sodium diet in sensitive rats.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037722-05
Application #
3353683
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1987-07-01
Project End
1994-03-30
Budget Start
1992-03-31
Budget End
1993-03-30
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294

  Publications

Carlson, Scott H; Wyss, J Michael (2011) Mechanisms underlying hypertension and obesity: a melanocortin linkage in the brain. Hypertension 57:375-6
Prasain, J K; Carlson, S H; Wyss, J M (2010) Flavonoids and age-related disease: risk, benefits and critical windows. Maturitas 66:163-71
Peng, Ning; Clark, John T; Wei, Chi-Chang et al. (2003) Estrogen depletion increases blood pressure and hypothalamic norepinephrine in middle-aged spontaneously hypertensive rats. Hypertension 41:1164-7
Roysommuti, Sanya; Mozaffari, Mahmood S; Wyss, J Michael (2003) Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive rats: role of sympathoexcitation. Can J Physiol Pharmacol 81:1036-41
Peng, Ning; Chambless, Brandon D; Oparil, Suzanne et al. (2003) Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus. Hypertension 41:571-5
Carlson, Scott H; Oparil, Suzanne; Chen, Yiu-Fai et al. (2002) Blood pressure and NaCl-sensitive hypertension are influenced by angiotensin-converting enzyme gene expression in transgenic mice. Hypertension 39:214-8
Carlson, S H; Roysomutti, S; Peng, N et al. (2001) The role of the central nervous system in NaCl-sensitive hypertension in spontaneously hypertensive rats. Am J Hypertens 14:155S-162S
Fang, Z; Carlson, S H; Chen, Y F et al. (2001) Estrogen depletion induces NaCl-sensitive hypertension in female spontaneously hypertensive rats. Am J Physiol Regul Integr Comp Physiol 281:R1934-9
Fang, Z; Carlson, S H; Peng, N et al. (2000) Circadian rhythm of plasma sodium is disrupted in spontaneously hypertensive rats fed a high-NaCl diet. Am J Physiol Regul Integr Comp Physiol 278:R1490-5
Carlson, S H; Wyss, J M (2000) Long-term telemetric recording of arterial pressure and heart rate in mice fed basal and high NaCl diets. Hypertension 35:E1-5

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