Thirst-mediated drinking behavior, in concert with arginine vasopressin (AVP)-mediated antidiuresis, are the fundamental systems maintaining body water volume and tonicity. Primary dipsogenic responses are mediated via plasma or cerebrospinal fluid hyperosmolality (OSM) and angiotensin II (AII), acting at select cerebral regions lacking a blood-brain barrier. Spontaneous fetal swallowing occurs early during ontogeny and has important roles in amniotic fluid homeostasis, fetal gastrointestinal development, and perhaps fetal somatic growth and maturation. Near term, both systemic and central dipsogenic mechanisms are functional in the ovine fetus, and thus are likely influenced and perhaps imprinted during gestation. We hypothesize: (1) Fetal responses to putative dipsogens (OSM, AII) mature (""""""""switch-on"""""""") acutely during the last third of gestation, reflecting maturation of integrated neural mechanisms, and (2) The development of endocrine (AVP; atrial natriuretic peptide family, ANP) modulation of OSM and AII dipsogenic responses is coincident with the onset of specific AVP and ANP receptor binding in cerebral regions regulating dipsogenic responses. Experiments are proposed to characterize the ontogeny of fetal dipsogenic responses to systemic and central OSM and AII, the modulation of dipsogenic responses by AVP and ANP, and the selective action of AVP, AMP and AII receptor subtypes. Central dipsogenic responses will be examined with both AII and OSM microinjections and stereotaxic lesions of select cerebral nuclei, and the maturation and endocrine modulation of dipsogenic responses will be correlated with ontogenic changes in cerebral AII, AVP and AMP receptor binding. In addition to swallowing, other neurobehavioral (electrocortical, """"""""breathing"""""""") activities, fetal cardiovascular parameters and plasma endocrine responses will be monitored in all studies. This combination of physiologic and endocrine approaches and the examination of select cerebral nuclei function will provide important new information, in a precocial species, concerning the in utero maturation of dipsogenic mechanisms essential for extrauterine fluid homeostasis.
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| 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 |
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