Effects of intracerebroventricular losartan on angiotensin II‐mediated pressor responses and <i>c‐fos</i> expression in near‐term ovine fetus

Shi, Lijun; Mao, Caiping; Thornton, Simon N.; Sun, Wanping; Wu, Jiawei; Yao, Jiaming; Xu, Zhice

doi:10.1002/cne.20802

Cited by 16 publications

(12 citation statements)

References 49 publications

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“…However, functional experiments do not support this postulation. As we indicated above, in the ovine fetus both central and peripheral administration of Ang II elicited a significant increase in blood pressure 26;60 which was completely abolished by the AT1R blocker losartan, but not by the AT2R blocker PD123319 21;25 . These findings directly contradict the data derived from binding assays that the AT2R is the predominant Angiotensin II receptor subtype in fetal life 3;4 .…”

Section: Discussionmentioning

confidence: 60%

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Gao

Chao

Parbhu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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In the current experiment, we determined AT2R and AT1R protein expression by Western blot analysis in developing normal mice. The results indicate that, (1) in all detected brain regions and in the spinal cord, adult mice exhibited significantly higher AT2R expression and lower AT1R expression in total protein extracts compared to fetuses and neonates; (2) other major organs, including heart, lung, liver, and kidney, exhibited the same expression pattern as the brain and spinal cord; (3) reciprocal changes in AT2R and AT1R expression were found in the total protein extracts from the brainstems of mice from one day prenatal to six weeks of age. There was a negative correlation between AT2R and AT1R protein expression; (4) in both membrane and cytosolic fractions from the brainstem, adult mice exhibited higher AT2R and lower AT1R expression than did fetuses and neonates; (5) in the brainstem, there were no significant differences in AT2R and AT1R mRNA levels among fetal, neonatal, and adult mice. The above results reconfirmed our previous finding in rats that adult animals have higher AT2R and lower AT1R expression compared to fetuses and neonates. These data imply an involvement of AT1R in fetal development and of AT2R in adult function.

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Section: Discussionmentioning

confidence: 60%

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Gao

Chao

Parbhu

et al. 2012

J Renin Angiotensin Aldosterone Syst

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“…However, functional data obtained from in vivo experiments document AT1R-mediated responses in the fetal brain, which supports our findings. For example, in ovine fetus, Zu and colleagues find that intracerebroventricular (icv) injection of Ang II evoked a significant increase in mean arterial blood pressure, 12,46 which was completely abolished by the AT1R blocker Losartan, but not by the AT2R antagonist PD123319, 10,45 suggesting the AT1R is the predominant receptor even in the fetus.…”

Section: Discussionmentioning

confidence: 99%

“…In most states, the AT1R is the predominant receptor subtype and masks the functions of the AT2R. Indeed, both central [10][11][12] and peripheral 13 administration of Ang II in fetal and adult animals evokes a pressor response, a typical effect of AT1R stimulation. On the other hand, the effects of AT2R activation emerge only after administration of Ang II plus an AT1R blocker, 14 or selective AT2R agonists such as CGP42112 15 and compound 21.…”

Section: Introductionmentioning

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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“…We have shown that exogenous Ang II-induced cardiovascular and AVP responses may be mediated by AT 1 Rs, since these responses can be blocked by lorsartan (a selective AT 1 R blocker) but not PD123319 (AT 2 receptor selective blocker) (28,29), and reported intense AT 1 R immunoreactivity in the fetal PVN and SON (36) with high expression of AT 1 R mRNA and its protein in the fetal hypothalamus by 70% gestation in sheep fetuses (12). In the present study, immunohistochemistry and double labeling were employed to show the colocalization of AT 1 R and c-fos expression in both SON and PVN following icv Ang I.…”

Section: Discussionmentioning

confidence: 98%

Central angiotensin I increases fetal AVP neuron activity and pressor responses

Shi

Mao

Zeng

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Angiotensin (Ang) II plays a critical role in cardiovascular homeostasis and neuroendocrine regulation. Little is known about whether central angiotensin-converting enzyme (ACE) is functional in the fetal brain. We investigated cardiovascular and neuroendocrinological responses to intracerebroventricular (icv) application of Ang I in the chronically prepared near-term ovine fetus in utero and examined the action sites marked by c-fos expression in the fetal hypothalamus. ACE mRNA was detected in the specific central areas. Intracerebroventricular Ang I significantly increased fetal blood pressure and c-fos expression in the supraoptic nuclei (SON) and the paraventricular nuclei (PVN) in the hypothalamus, accompanied by an increase of fetal plasma arginine vasopressin (AVP). Double labeling demonstrated that AVP neurons in the fetal SON and PVN were expressing c-fos. Captopril, an inhibitor of ACE, significantly suppressed fetal pressor responses and plasma AVP. Double labeling experiments showed colocalization of AT(1) receptor (AT(1)R) and c-fos expression in both SON and PVN following icv Ang I. The results indicate that central endogenous ACE has been functional at least at the last third of gestation and the endogenous brain renin-angiotensin system-mediated pressor responses and AVP release via AT(1)Rs by acting at the sites consistent with the cardiovascular network in the hypothalamus.

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Effects of intracerebroventricular losartan on angiotensin II‐mediated pressor responses and c‐fos expression in near‐term ovine fetus

Cited by 16 publications

References 49 publications

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Ontogeny of angiotensin type 2 and type 1 receptor expression in mice

Developmental expression patterns for angiotensin receptors in mouse skin and brain

Central angiotensin I increases fetal AVP neuron activity and pressor responses

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