Recent work of this laboratory shows that separation of infant rats from their dam for periods of 6 to 8 hours predisposes them to increased NaCl intake in adulthood. The increased intake is expressed both when the animals are sodium deficient and when they are need-free. That is, they drink more 3% NaCl both in the immediate aftermath of acute sodium depletion and while they are in positive sodium balance and have no meta- bolic need for the ingested sodium. The elevated need-free salt intake persists for the life of the animal, and is greater in females, despite the ingestion of sodium-rich commercial food, and despite the absence of renal pathology or of alterations in the plasma levels of the hormones of renal sodium conservation (angiotensin 11 and aldosterone). It is, in other words, an animal model of chronic salt overconsumption in man. The proposed experiments will investigate the biological basis of the phenomenon by: 1. Specifying the most effective aspect of the maternal separation. 2. Describing the age of its onset. 3. Testing the adult consequences of repeated neonatal treatments. 4. Testing the possibility that it is a result of the operation in infancy of the angiotensin/aldosterone synergy that is the basis of salt appetite in the adult rat. 5. And, continuing the studies of the suppression of salt intake by the tachykinins with emphasis on the ontogeny of their antinatrorexic effects. This research is relevant to a significant public health and medical problem. Sodium overconsumption is common in our population. A lifetime of excess salt ingestion puts cardiovascular and renal health at risk. Basic research on the ontogeny of salt intake could result in rational chemotherapies for salt overconsumption, and in improved infant nutritional practices that would discourage excess salt ingestion later in life.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025857-02
Application #
3327068
Study Section
Biopsychology Study Section (BPO)
Project Start
1989-08-01
Project End
1994-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Galaverna, O; Nicolaidis, S; Yao, S Z et al. (1995) Endocrine consequences of prenatal sodium depletion prepare rats for high need-free NaCl intake in adulthood. Am J Physiol 269:R578-83
Yee, D K; Reagan, L P; Moga, C N et al. (1994) Angiotensin II stabilizes a multimeric type 2 (AT2) receptor complex in murine neuroblastoma N1E-115 cells. Regul Pept 54:355-66
Siemens, I R; Reagan, L P; Yee, D K et al. (1994) Biochemical characterization of two distinct angiotensin AT2 receptor populations in murine neuroblastoma N1E-115 cells. J Neurochem 62:2106-15
Reagan, L P; Theveniau, M; Yang, X D et al. (1993) Development of polyclonal antibodies against angiotensin type 2 receptors. Proc Natl Acad Sci U S A 90:7956-60
Leshem, M; Langberg, J; Epstein, A N (1993) Salt appetite consequent on sodium depletion in the suckling rat pup. Dev Psychobiol 26:97-114
Epstein, A N (1992) Control of salt intake by steroids and cerebral peptides. Pharmacol Res 25:113-24
Thompson, C I; Epstein, A N (1991) Salt appetite in rat pups: ontogeny of angiotensin II-aldosterone synergy. Am J Physiol 260:R421-9
Frankmann, S P; Ulrich, P; Epstein, A N (1991) Transient and lasting effects of reproductive episodes on NaCl intake of the female rat. Appetite 16:193-204
Epstein, A N (1991) Neurohormonal control of salt intake in the rat. Brain Res Bull 27:315-20