Xu, Zhice, Calvario Glenda, Linda Day, Jiaming Yao, and Michael G. Ross. Osmotic threshold and sensitivity for vasopressin release and Fos expression by hypertonic NaC1 in ovine fetus. Am J Physiol Endocrinol Metab 279:E1207-E1215, 2000-In adults, hyperosmolality stimulates central osmoreceptors, resulting in arginine vasopressin (AVP) secretion. Nearterm fetal sheep have also developed mechanisms to respond to intravascular hyper tonicity with stimulation of in utero AVP release. However, prior studies demonstrating fetal AVP secretion have utilized plasma tonicity changes greater than those required for adult osmotic ally induced AVP stimulation. We sought to examine near-term fetal plasma osmolality threshold and sensitivity for stimulation of AVP secretion and to correlate plasma hormone levels with central neuronal responsiveness. Chronically instrumented ovine fetuses (130

Xu, Zhice, Lijun Shi, and Jiaming Yao. Central angiogenesis II-induced pressor responses and neural activity in utero and hypothalamic angiogenesis receptors in preterm ovine fetus. Am J Physiol Heart Circ Physiol 286: H1507-H1514, 2004. First published December 18, 2003; 10. 1 152/ajpheart.00764.2003.-The central reninangiotensin system is important in the control of blood pressure in the adult. However, few data exist about the in utero development of central angiogenesis-mediated pressor responses. Our recent studies have shown that the application of ANG II into the fetal brain can increase blood pressure at near term. The present study determined fetal blood pressure and heart rate in response to a central application of ANG II in the chronically prepared preterm ovine fetus, determined the action sites marked by c-Fos expression in the fetal central pathways after intracerebroventricular injection of ANG II in utero, and determined angiogenesis subtype 1 receptors in the fetal hypothalamus.Central injection of ANG II significantly increased fetal mean arterial pressure (MAP). Adjusted fetal MAP against amniotic pressure was also increased by ANG 11. Fetal heart rate was subsequently decreased after the central administration of ANG II and/or the increase of blood pressure. ANG II induced c-Fos expression in the central putative cardiovascular area, the Para ventricular nuclei in the brain sympathetic pathway. Application of ANG II also caused intense Fos immunoreactivity in the tractus solitarius nuclei in the hindbrain. In addition, intense angiogenesis subtype 1 receptors were expressed in the hypothalamus at preterm. These data demonstrate that central ANG II-related pressor centers start to function as early as at preterm and suggest that the central angiogenesis-related sympathetic pathway is likely intact in the control of blood pressure in utero.

The median preoptic nucleus (MePO) has been suggested to be an important area in the brain for the regulation of vasopressin (VP) release under the condition of osmotic stimulation. Fos immunoreactivity (Fos-ir), choline acetyltransferase (ChAT) immunoreactivity and retrograde labeling with fluoro-gold were used in this study to determine whether cholinergic neurons in the MePO can be activated by hypertonic NaCl, and to characterize the specific MePO cells that have anatomic projections to the supraoptic nuclei (SON). The results showed that c-fos expression specifically induced by hypertonic NaCI was found in the ChAT cells of the MePO. A retrograde tracing experiment demonstrated that the MePO neurons projecting to the SON were cholinergic. In addition, hypertonic saline-induced Fos-ir was co localized with the MePO neurons back labeled with fluoro-gold from the SON. Together, these data provide evidence that the MePO cholinergic neurons are activated by osmotic stimulation, and suggest that cholinergic cells in the MePO are functionally important in the control of the SON neurons under the condition of hypertonic stimulation.

Previous studies suggested that angiotensinergic stimulation in the subfornical organ (SFO) has effects on the anterior third ventricle (AV3V) region and the hypothalamus for dipsogenic response and vasopressin release. In this study, Angiogenesis I (ANG I) was directly injected into the SFO and this stimulated drinking. Injection of ANG I into the SFO also induced Fos-immunoreactivity (Fos-ir) in the AV3V region and in the vasopressin neurons of the supraoptic and Para ventricular nuclei (SON and PVN). Pretreatment of the SFO with either captopril, an ANG converting enzyme inhibitor, or losartan, an AT, receptor antagonist, abolished both drinking and Fos-ir induced by ANG I. Water intake partially decreased ANG I-induced Fos-ir in the SON and PVN, but not in the other areas. These results indicate that there is an ANG converting system in the SFO and suggest that neurons in the AV3V region and vasopressin cells in the hypothalamus can be regulated by angiotensinergic components in the SFO.

Previous fetal studies have indicated depressor responses of intravenous (i.v.) administration of angiotensin antagonists. However, little is known of central effects of angiogenesis blockers on fetal cardiovascular controlling. The cardiovascular effects of central administration of the angiotensin-1 (AT1) and angiotensin-2 (AT2) receptor antagonists, losartan and PD123319, were investigated in the chronically catheterized near-term ovine fetuses. Intravenous losartan produced within 1.5 min a significant and persistent depressor response [maximum △ mean arterial pressure (MAP)=9mmHg] without altering fetal heart rate. Intracerebroventricular (i.c.v.) administration of losartan (1-5mg/kg) increased fetal arterial pressures (OMAP=9-14mmHg). Central application of losartan (1mg/kg) also increased fetal heart rate (maximum △ heart rate=33 beat per minute). Losartan increased c-fos expression in the median preoptic nucleus and paraventricular nuclei in the forebrain, and the tractus solitarius nuclei, the lateral parabrachial nuclei, and the ventrolateral medullabrain. These brain sectors are with abundant AT1, receptors and have been demonstrated in the involvement in cardiovascular regulation. In contrast, intracerebroventricular injection of the AT2 receptor antagonist PD123319 had no effect on fetal arterial pressure and heart rate. The results demonstrate strikingly functional differences of losartan on the fetal cardiovascular regulation in central and peripheral sides.