Central cholinergic mechanisms play important roles in the control of cardiovascular responses. However, in utero development of brain cholinergic mechanism in regulation of arterial pressure before birth is largely unknown. This study investigated cardiovascular responses to central application of carbachol in fetuses and determined functional development of the central cholinergic systems controlling fetal pressor responses in utero. Chronically prepared near-term ovine fetuses (90% gestation) received an injection of carbachol intracerebroventricularly (i.c.v.). Fetal cardiovascular responses were measured, and the brains were used for c-fos mapping studies. In response to carbachol injection i.c.v., fetal systolic, diastolic, and mean arterial pressure (MAP) immediately increased, accompanied by a bradycardia. The maximum increase of MAP was at 30 min after the i.c.v. injection of carbachol and lasted 90 min. Associated with the pressor response, the neuronal activity marked with c-fos was enhanced significantly in the fetal anterior third ventricle (AV3V) region (including the median preoptic nucleus and organum vasculosum of the lamina terminalis) in the forebrain, and in the area postrema, lateral parabrachial nucleus, nucleus tractus solitary, and rostra) ventrolateral medulla in the hindbrain. These results indicate that the central cholinergic mechanism is functional in the control of fetal blood pressure at the last third of gestation, and the central AV3V region and hindbrain have been intact relatively during in utero development in sheep at 90% gestational stage. Neuropsychopharmacology advance online publication, 20 April 2005; doi:10.I038/sj.npp. 1300738 developmental neurobiology;

AVP not only influences renal water excretion but also has profound cardiovascular effects in adults. Our recent studies have demonstrated that central angiogenesis induced fetal pressor responses accompanied with AVP release. However, little is known of hormonal mechanisms in angiogenesis-mediated fetal blood pressure (BP) changes. The present study determined AVP mechanisms in central angiogenesis-mediated fetal pressor responses. The V1-receptor antagonist or V2-receptor antagonist was infused intravenously into the ovine fetus at 90% gestation. Angiogenesis II (Ang II; 1.5