The proposed studies investigate the combined effects of two variables behavior stress and excess sodium intake- that have been highly implicated in the loss of regulatory control of blood pressure (BP) leading to hypertension. The project will study normotensive baboons before, during and after six months of exposure to daily behavioral stress sessions combined with daily ingestion of excess dietary sodium. Controls will receive stress only. Additionally, baboons with one renal artery constricted will be exposed to stress without excess sodium. Salt will be administered by training subjects to ingest hypertonic saline (8.6 mEq Na/kg/day) in juice. Behavioral stress will make use of two known effective procedures, where previously trained behaviors are no longer successful in obtaining food (extinction), and, where food acquisition behaviors produce a mild electric shock (conflict). Both stress components will occur unpredictably during portions of daily experimental sessions. Stage 1 will assess, BP, heart rate, and levels of the neuroendocrine substances catecholamines and metabolites, renin activity and aldosterone, 17-hydroxycorticosteroids, atrial natriuretic peptide, and other regulatory and electrolyte levels. Left ventricular mass may increase after six months of BP elevation due to the stress sodium combination; this will be assessed with use of nuclear magnetic resonance (MRI) imaging of the heart. If the stress and sodium combination in Stage 1 chronically increases BP in healthy baboons by at least 15 mmHg, and if stress exacerbates the already existing hypertension in the renovascular monkeys, stage 2 will include study of: the relative contributions of given amounts of salt and/or stress to the hypertension; means to enhance the salt-stress effect, including manipulations of predictability and controllability of the behavioral stress schedule; and, pathophysiologic mechanisms inferred from relative responsiveness to antihypertensive treatments and from blood levels of neuroendocrine substances. If the Stage 1 data show that the salt-stress combination does not chronically increase BP in the baboon, then Stage 2 will assess whether the addition of deoxycorticosterone acetate (DOCA) will enhance the stress-sodium combination, and, will enhance the effects of stress in renovascular hypertensive baboons. Those parameters found to be optimal in producing BP elevations will be used in a new cohort of baboons in Years 3-5. Throughout, MRI imaging of the heart will be repeated 3/year for experimental and control subjects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL040138-01
Application #
3357246
Study Section
(SRC)
Project Start
1987-09-30
Project End
1992-07-31
Budget Start
1987-09-30
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218