Epidemiological studies have enumerated a host of variables that seem to play a role in the development of essential hypertension in humans, including genetics, high sodium intake, exercise (and its relationship to obesity), and societal stress. It has, of course, been difficult to determine precisely what role each of these variables plays in essential hypertension due to the presence of a mixture of variables within a given population or sub- population. It is even more difficult to study life-span changes in populations or to determine the mechanisms which relate genetic and environmental variables to chronic alterations in physiological and biochemical function. Animal models afford the opportunity to perform long-term studies in a short time, and thus offer a means to study the mechanisms by which genetic and environmental variables produce hypertension. While there has been an adequate genetic model for hypertension for a number of years (the spontaneously hypertensive rat, or SHR), there is no suitable animal model for studying the range of environmental variables thought to be related to the development of essential hypertension in humans. Our laboratory has recently developed such a model, which we call the borderline hypertensive rat (BHR). The BHR has one hypertensive and one normotensive parent. The mixed genetic background seems more relevant to human essential hypertension than previous models, which have focused on animals with long histories of normotension or hypertension. A number of hypotheses relating the interactions between dietary sodium intake, tail shock stress, exercise and genetic history of hypertension will be tested in animals - with either no parental history of hypertension (normotensive parents), a mixed parental history (BHR), or a strong parental history (SHR) - studied for 4, 8, or 16 months. The major dependent variables will assess CNS/renal interactions in the development of chronic changes in blood pressure. Specifically, terminal experiments at the appropriate ages will include metabolic studies, assessment of renal function (GFR and RPF), direct blood pressure in resting animals, plasma assays for catecholamines, corticosterone, PRA, AVP, and ANP, as well as catecholamine levels in discrete brainstem and hypothalamic nuclei, using the Palkovits micropunch technique. These data will answer questions related to the physiological and biochemical mechanisms of environmentally- induced hypertension, especially as they relate to """"""""family history.""""""""

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL019680-10
Application #
3335895
Study Section
Biopsychology Study Section (BPO)
Project Start
1978-07-01
Project End
1992-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Tennessee Knoxville
Department
Type
Schools of Arts and Sciences
DUNS #
City
Knoxville
State
TN
Country
United States
Zip Code
37996
Brown, D R; Li, S G; Lawler, J E et al. (1999) Sympathetic control of BP and BP variability in borderline hypertensive rats on high- vs. low-salt diet. Am J Physiol 277:R650-7
Li, S G; Lawler, J E; Randall, D C et al. (1997) Sympathetic nervous activity and arterial pressure responses during rest and acute behavioral stress in SHR versus WKY rats. J Auton Nerv Syst 62:147-54
Lawler, J E; Zheng, G; Li, S et al. (1996) Norepinephrine levels in discrete brain nuclei in borderline hypertensive rats exposed to compound stressors. Brain Res Bull 41:87-92
Golden, A L; Bright, J M; Lawler, J E (1994) Changes in creatine kinase expression induced by exercise in borderline hypertensive rat hearts. Clin Exp Hypertens 16:577-93
Lawler, J E; Abel, M M; Naylor, S K (1993) Effects of salt intake on blood pressure and heart rate responses to footshock stress in SHR, BHR, and WKY rats. Physiol Behav 53:97-102
Lawler, J E; Naylor, S K; Abel, M M (1993) Predictability of foot shock differentially affects the phasic blood pressure of SHR, BHR, and WKY rats. Physiol Behav 54:369-74
Lawler, J E; Naylor, S K; Abel, M M et al. (1993) A chronic high-salt diet fails to enhance blood pressure reactivity to a tone associated with footshock in SHR, BHR, and WKY rats. Physiol Behav 54:941-6
Lawler, J E; Sanders, B J; Cox, R H et al. (1991) Baroreflex function in chronically stressed borderline hypertensive rats. Physiol Behav 49:539-42
Lawler, J E; Sanders, B J; Cox, R H et al. (1989) Bilateral renal denervation can prevent the development of stress-induced hypertension in the borderline hypertensive rat. Clin Exp Hypertens A 11:1549-63
Mitchell, V P; Lawler, J E (1989) Norepinephrine content of discrete brain nuclei in acutely and chronically stressed borderline hypertensive rats. Brain Res Bull 22:545-7

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