Six months of social stress of mice living in complex population cages gives chronic neuroendocrine arousal leading to high blood pressure, arteriosclerosis, myocardial fibrosis and elevated plasma renin together with chronic interstitial nephritis found only in vigorously competing animals. To study the effect of low salt diet on this chronic psychosocial hypertension, we developed a grain based diet Purina-USC 5717C-19 which contains Less than 5 gms NaCl/70kg/day yet supports competing mice without losses. In preliminary work this diet has not prevented hypertension. However the high blood pressure is chronically controlled by B adrenergic blockade with Metoprolol and acutely by the angiotensin blocker, Captopril. Renal failure develops in spite of this control of blood pressure. The mechanism of this interstitial nephritis may be reflux but remains undetermined. Our measures include bi-weekly or monthly: Blood pressure, pulse rate, body weight and scarring; plasma and renins corticosterone at intervals and at termination heart, adrenal, kidney and seminal vesicle weights as well as adrenal tyrosine hydroxylase and heart and kidney pathology. Our current goals are to determine if a low salt diet does indeed fail to control hypertension; to study the antihypertensive effects of the thiazide diuretic, Enduron and of the long term use of Captopril (both drugs to be given with and without the low salt diet). We will also continue to supply stressed mice for: (1) the study of increased vascular sensitivity to angiotensin II discovered by Webb et al in psychosocial hypertension, (2) the study of aspirin plus caffeine plus stress by Bennett and (3) the chronic interstitial and Tam Horsfall protein immune response by Fasth. We will make pilot studies of neuroendocrine differentiation of dominants from subordinates in relation to a high renin-sympathetic, low renin-corticoid dichotomy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL030129-04
Application #
3341180
Study Section
Biopsychology Study Section (BPO)
Project Start
1982-07-01
Project End
1988-07-31
Budget Start
1985-12-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Loma Linda University
Department
Type
Schools of Medicine
DUNS #
City
Loma Linda
State
CA
Country
United States
Zip Code
92350