Intravenous angiotensin induces brain c-fosexpression and vasopressin release in the near-term ovine fetus

Abstract

2003.-The effect of intravenous angiotensin II (ANG II) on fetal brain c-fos expression and arginine vasopressin (AVP) release was studied in the near-term ovine fetus. Fetuses with chronically implanted catheters received an intravenous infusion of ANG II or saline. Fetal plasma AVP concentrations were significantly increased after the peripheral administration of ANG II, with peak levels (3-fold) at 30 min after the intravenous infusion. There was no change in fetal plasma osmolality, sodium, and hematocrit levels between the control and experimental groups or between the periods before and after the infusion of ANG II. Intravenous ANG II administration induced Fos immunoreactivity (Fos-IR) in the circumventricular organs and the median preoptic nucleus of the fetal brain. Fos-IR was also demonstrated in the fetal supraoptic nuclei (SON). Double labeling demonstrated that the AVP-containing neurons in the SON were expressing c-fos in response to intravenous ANG II. These results indicate that the peripheral ANG II in the fetus may play a significant role in stimulating the central hypothalamic-neurohypophysial system during late gestation. It supports the hypothesis that circulating ANG II may act at the fetal AVP neurons in the hypothalamus in body fluid balance via the circumventricular organs, which are situated outside the blood-brain barrier, and the central neural pathway between these two brain structures has been relatively established in utero, at least at near-term. angiotensin II; fetal brain development; arginine vasopressin NUMEROUS EARLIER STUDIES have shown that the central renin-angiotensin system (RAS) is as important as peripheral RAS in the control of body fluid and cardiovascular homeostasis. In adults, there is significant information regarding the effects of central and peripheral angiotensin (ANG) (8, 21). Administration of either ANG II or its precursors into the brain or the peripheral bloodstream produces a pressor response, induces drinking behavior, and causes release of adrenocorticotropic hormone and arginine vasopressin (AVP) (1,8,25). A link between peripheral administration of ANG II and AVP release in adult animals has been well established (9). The effect of intravenous ANG II on the hypothalamic-neurohypophysial system has been suggested via circumventricular organs (CVOs), which lack blood-brain barriers (BBB) (28). Furthermore, blockade of the ANG receptors can suppress AVP release into the circulation (3). Although there are a number of studies that have demonstrated the importance of ANG mechanisms in the regulation of AVP in adults, very little is known about the relationship between peripheral ANG and central AVP systems in the fetus. Addressing this question is important not only to prenatal life but also to postnatal health.Previous fetal studies have demonstrated that an active RAS is present in the fetus before birth, and ANG II has been ascribed important functions in the fetus (11,13,14). Its major function appears to be maintenance of fetal arterial pressure und...

AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

“…AT1R and AT2R play an important role in cell growth, differentiation and apoptosis during development 13–16 . Abnormal AT1R and AT2R expression in the renal system has also been shown to be related to kidney diseases 17,18 . However, the detailed mechanism underlying Ang II-induced renal tubular cell necroptosis and kidney injuries is not fully understood.…”

Development of fetal brain renin–angiotensin system and hypertension programmed in fetal origins

“…However, several central regions, including the SFO, OVLT, and AP, lack a BBB, thus Ang II in the peripheral circulation can act on the brain via those central “windows”. In a recent study in the sheep, we demonstrated that intravenous Ang II can induce cellular activity marked with intensive c-fos expression in the SFO, OVLT, MnPO, SON, and PVN (Shi et al, 2003, 2004c). The peripheral Ang II acts on the fetal hypothalamus indirectly via the circumventricular organs (CVOs, such as SFO, OVLT in the forebrain) which lack the BBB, but are rich of Ang II receptors.…”

The Renin-Angiotensin System in Conscious Newborn Sheep: Metabolic Clearance Rate and Activity

“…Moreover, as in fetal sheep (11), arterial ANG II infusions in the newborn hind limb do not elicit vasoconstrictor responses (17), suggesting that ANG II-induced pressor responses after birth occur through indirect mechanisms, e.g. release of AVP or catecholamines (34,35). However, Wilson et al (21) reported that increases in circulating ANG II after birth contributed to the increase in MAP.…”