Thirst and swallowing represent a fundamental biologic system for the regulation of body water homeostasis. In-utero swallowing, modulated by fetal """"""""thirst"""""""" and electrocortical state, results in the resorption of amniotic fluid water, electrolytes and endocrine factors. During the perinatal period, imprinting of hormonal and physiologic factors regulating thirst may permanently alter adult fluid balance. Therefore, the study of fetal """"""""thirst"""""""" and swallowing can contribute to an understanding of the development of mechanisms for fluid regulation. In addition, analysis of patterns of esophageal fluid flow and fetal behavioral states may provide insight into the association of neonatal thirst, regurgitation and altered breathing patterns. Spontaneous and thirst-mediated swallowing behavior develop and mature in-utero in sheep and humans. Thus, a fetal model is necessary to investigate the ontogenesis of thirst regulation. We have developed a chronic ovine fetal model for the quantification of swallowing activity and volume and the simultaneous determination of fetal behavioral state. We have demonstrated that, similar to the adult, fetal swallowing both occurs spontaneously and can be stimulated by dipsogenic factors. However, fetal responses to known dipsogenic stimuli may differ from the adult. Furthermore, spontaneous fetal swallowing activity may be suppressed in accordance with behavioral state alterations. This project will characterize the ontogeny of spontaneous fetal swallowing, the presence of diurnal rhythms and the association with fetal behavioral state maturation. The ontogeny of fetal swallowing stimulation by primary systemic stimuli (hyperosmolality and angiotensin II; AII) and the modulation by arginine vasopressin (AVP) and atrial natriuretic factor (ANF) will be studied. The receptor mediation of AII and AVP stimulated swallowing will be probed with selective receptor antagonists. In addition, the central stimulation and suppression of swallowing by primary endocrine factors (AII, AVP, ANF) will be explored. The ovine model offers the opportunity to study, in a precocial species, the ontogeny of """"""""thirst"""""""" physiology, an important but relatively unexplored area of perinatal physiology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK043311-02
Application #
3244679
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1991-08-01
Project End
1994-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
City
Torrance
State
CA
Country
United States
Zip Code
90502
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Mansano, Roy; Desai, Mina; Garg, Ambica et al. (2007) Enhanced nephrogenesis in offspring of water-restricted rat dams. Am J Obstet Gynecol 196:480.e1-6
Ross, Michael G; Desai, Mina; Khorram, Omid et al. (2007) Gestational programming of offspring obesity: a potential contributor to Alzheimer's disease. Curr Alzheimer Res 4:213-7
Gayle, Dave A; Desai, Mina; Casillas, Ederlen et al. (2006) Gender-specific orexigenic and anorexigenic mechanisms in rats. Life Sci 79:1531-6
El-Haddad, Mostafa A; Chao, Conrad R; Ross, Michael G (2005) N-methyl-D-aspartate glutamate receptor mediates spontaneous and angiotensin II-stimulated ovine fetal swallowing. J Soc Gynecol Investig 12:504-9
El-Haddad, Mostafa A; Ismail, Yaser; Gayle, Dave et al. (2005) Central angiotensin II AT1 receptors mediate fetal swallowing and pressor responses in the near-term ovine fetus. Am J Physiol Regul Integr Comp Physiol 288:R1014-20
Ross, Michael G; Desai, Mina (2005) Gestational programming: population survival effects of drought and famine during pregnancy. Am J Physiol Regul Integr Comp Physiol 288:R25-33
El-Haddad, Mostafa A; Jia, Yousheng; Ross, Michael G (2005) Persistent sucrose stimulation of ovine fetal ingestion: lack of adaptation responses. J Matern Fetal Neonatal Med 18:123-7
El-Haddad, M A; Ismail, Y; Day, L et al. (2004) Unopposed appetite (orexigenic) mechanisms in the near-term ovine fetus: central leptin does not inhibit sucrose ingestion. J Matern Fetal Neonatal Med 15:291-6

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