The AT2 angiotensin receptor subtype predominates in the 18 day gestation fetal rat brain

Cook, Vickie I.; Grove, Kevin L.; McMENAMIN, K. M.; Carter, Michele R.; Harding, Joseph W.; Speth, Robert C.

doi:10.1016/0006-8993(91)91254-x

Cited by 38 publications

(19 citation statements)

References 18 publications

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“…In our isolated embryonic neuron system, a clear effect of A II on both neuropeptides secretion was found, thus indicating a clear neurotrophic effect. This event is strongly supported by studies indicating that specific A II receptors (types 1 and 2) are already present in brain areas of embryos from late gestating rats [21,22]. The A II dipsogenic effect takes place to maintain water homeostasis by activating neurons present in several brainstem sites including the PVN-SON [35].…”

Section: Discussionmentioning

confidence: 76%

“…Moreover, A II shows neuropeptide releasing activity upon A II-sensitive hypothalamic neurons, stimulating both AVP and OT output [20]. Although specific A II receptors are already expressed during late embryonic life [21,22], specific information regarding any in vitro A II effect on embryonic magnocellular neuron survival and function is still lacking.…”

Section: Introductionmentioning

confidence: 99%

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In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

Moreno

Piermaria

Gaillard

et al. 2010

Endocr

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There are only a few studies on the ontogeny and differentiation process of the hypothalamic supraoptic-paraventriculo-neurohypophysial neurosecretory system. In vitro neuron survival improves if cells are of embryonic origin; however, surviving hypothalamic neurons in culture were found to express small and minimal amounts of arginine-vasopressin (AVP) and oxytocin (OT), respectively. The aim of this study was to develop a primary neuronal culture design applicable to the study of magnocellular hypothalamic system functionality. For this purpose, a primary neuronal culture was set up after mechanical dissociation of sterile hypothalamic blocks from 17-day-old Sprague-Dawley rat embryos (E17) of both sexes. Isolated hypothalamic cells were cultured with supplemented (B27)-NeuroBasal medium containing an agent inhibiting non-neuron cell proliferation. The neurosecretory process was characterized by detecting AVP and OT secreted into the medium on different days of culture. Data indicate that spontaneous AVP and OT release occurred in a culture day-dependent fashion, being maximal on day 13 for AVP, and on day 10 for OT. Interestingly, brain-derived neurotrophic factor (BDNF) and Angiotensin II (A II) were able to positively modulate neuropeptide output. Furthermore, on day 17 of culture, non-specific (high-KCl) and specific (Angiotensin II) stimuli were able to significantly (P < 0.05) enhance the secretion of both neuropeptides over respective baselines. This study suggests that our experimental design is useful for the study of AVP- and OT-ergic neuron functionality and that BDNF and A II are positive modulators of embryonic hypothalamic cell development.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

Moreno

Piermaria

Gaillard

et al. 2010

Endocr

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“…Almost all of the known biological effects of ANG II are mediated by AT 1 receptors, whereas the exact physiological function of AT 2 receptors remains unclear. A previous study (7) has indicated that the rat fetus expresses more AT 2 than AT 1 receptors in the brain. Despite this, few data exist regarding the development of AT 1 receptors in the hypothalamus in the fetal brain, particularly at the preterm.…”

Section: Discussionmentioning

confidence: 93%

“…A number of studies have confirmed that almost all biological effects of ANG II are expressed via angiotensin subtype 1 (AT 1 ) receptors, not AT 2 receptors (21,31,32). It has been suggested that more AT 2 than AT 1 receptors exist in the fetal brain (7). Whether AT 1 receptors have developed in the fetal hypothalamus is understudied.…”

mentioning

confidence: 99%

Central angiotensin II-induced pressor responses and neural activity in utero and hypothalamic angiotensin receptors in preterm ovine fetus

Shi

Yao

2004

American Journal of Physiology-Heart and Circulatory Physiology

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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 angiotensin-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 angiotensin 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 II. 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 paraventricular 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 angiotensin 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 angiotensin-related sympathetic pathway is likely intact in the control of blood pressure in utero.in utero pressor; angiotensin type 1 receptor; developmental brain pathway ANGIOTENSIN II (ANG II) is a potent vasoconstrictive hormone, and a number of studies have demonstrated the importance of the renin-angiotensin system (RAS) in the control of blood pressure (BP) (1,19,23). Earlier work has shown that an active RAS is present in the ovine fetus before birth (6, 15). Its major function appears to be the regulation of fetal arterial pressure under conditions of fetal stress, including acute hemorrhage or hypoxia (17). However, study of the development of the central RAS in the regulation of BP in utero is still limited. Notably, most previous work performed in the fetus focused exclusively on actions of angiotensin at the peripheral side in the control of BP in utero (8,10,15,17,28). Our recent studies have demonstrated an increase of fetal mean arterial pressure (MAP) immediately after an injection of ANG II into the lateral ventricle of the near-term (90% gestational age) ovine fetal brain in utero (36). This observation prompted initial experiments investigating the cardiovascular action of fetal intracerebroventricular injection of octapeptide ANG II.In the adult, administration of either ANG II or its precursors into the brain induces pressor responses, drinking, and release of hormones (3,11,29). A number of studies have confirmed that almost all biological effects of ANG II are expressed via angiotensin subtype 1 (AT 1 ) receptors, not AT 2 receptor...

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“…The ontogeny of angiotensin II receptors therefore should be re-evaluated. The literature indicates that the general concept of AT2R maturation is primarily based on observations from autoradiography, [22][23][24][25] competitive ligand binding, [26][27][28][29] and in situ hybridization. [30][31][32][33] These experiments were carried out 20 years ago.…”

Section: Discussionmentioning

confidence: 99%

Developmental expression patterns for angiotensin receptors in mouse skin and brain

Shao

Gao

2012

J Renin Angiotensin Aldosterone Syst

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Two G-protein-coupled receptors, angiotensin type 1 receptor (AT1R) and type 2 receptor (AT2R), mediate the majority of angiotensin II (Ang II) effects. It has long been believed that the AT2R is reduced to extremely low levels in adulthood but is abundantly expressed in the fetus. However, recent data from rats and mice do not support this notion. Employing Western blot analysis, we found a gradual increase in AT2R protein expression from fetal life to adulthood in brain, heart, lung, liver, and kidney. The reason for the discrepancy between our observations and the conventional concept is unknown. Evidence supporting a regression of the AT2R during maturation is derived largely from autoradiographic signals that were confined to the outline of fetal rats, implying that the previously reported high AT2R expression in the fetus might be valid only for skin. We therefore hypothesized that the ontogeny of angiotensin receptors in skin is opposite that in other organs. In the current experiment, we employed Western blot analysis to compare AT2R and AT1R protein expressions in skin with that in the brainstem of fetal and adult mice. Fetal brainstem expressed lower AT2R and higher AT1R protein compared to adult brainstem (AT2R/GAPDH: 0.08 ± 0.2 in fetus vs 7.6 ± 0.9 in adult, p < 0.05; AT1R/GAPDH: 5.9 ± 0.8 in fetus vs 0.7 ± 0.3 in adult, p < 0.05). In contrast, fetal skin expresses higher AT2R and lower AT1R protein compared to adult skin (AT2R/GAPDH: 0.95 ± 0.4 in fetus vs 0.04 ± 0.2 in adult, p < 0.05; AT1R/ GAPDH: 0.6 ± 0.2 in fetus vs 2.1 ± 0.5 in adult, p < 0.05). This expression profile was also confirmed by immunofluorescence. Using real-time RT-PCR, we could not detect any significant differences in mRNA of these two receptors in brainstem between fetal and adult mice. However, we found a higher AT2R mRNA and lower AT1R mRNA in the fetal skin compared to adult skin. The above results confirm our hypothesis that skin displays an expression profile of angiotensin receptors opposite that of other organs during development, suggesting that the currently held view concerning AT2R maturation is suitable only for skin. In other organs and tissues, adults express higher AT2R protein than does the fetus.

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The AT2 angiotensin receptor subtype predominates in the 18 day gestation fetal rat brain

Cited by 38 publications

References 18 publications

In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

In vitro functionality of isolated embryonic hypothalamic vasopressinergic and oxytocinergic neurons: modulatory effects of brain-derived neurotrophic factor and angiotensin II

Central angiotensin II-induced pressor responses and neural activity in utero and hypothalamic angiotensin receptors in preterm ovine fetus

Developmental expression patterns for angiotensin receptors in mouse skin and brain

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