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| Item Type: | Article |
|---|---|
| Title: | Stress sensitivity is increased in transgenic rats with low brain angiotensinogen |
| Creators Name: | Mueller, H., Kroeger, J., Joehren, O., Szymczak, S., Bader, M., Dominiak, P. and Raasch, W. |
| Abstract: | Objective. AT1-blockers attenuate hypothalamo-pituitary-adrenal (HPA)-axis reactivity in hypertension independently of their potency to lower blood pressure. A reduced pituitary sensitivity to corticotropin-releasing hormone (CRH) and a down-regulation of hypothalamic CRH expression have been suggested to influence HPA-axis activity during chronic AT1-blockade. Design. This study was aimed at confirming the role of central angiotensin II in regulating HPA-reactivity by using the transgenic rat TGR(ASrAOGEN), a model featuring low levels of brain angiotensinogen. Different stress tests were performed to determine HPA-reactivity in TGR(ASrAOGEN) and appropriate controls. Results. In TGR(ASrAOGEN) blood pressure was diminished compared to controls. The corticosterone response to a CRH or adrenocorticotropic hormone (ACTH) challenge and a forced swim test (FST) was more distinct in TGR(ASrAOGEN) than it was in controls and occurred independently of a concurrent enhancement in ACTH. Using quantitative real time PCR we found increased mRNA-levels of MC2- and AT2-receptor in the adrenals of TGR(ASrAOGEN), whereas mRNA-levels of CRH, pro-opiomelanocortin (POMC) and AT1-receptors remained unchanged in hypothalami and pituitary glands. Conclusions. Since stress responses were increased rather than attenuated in TGR(ASrAOGEN), we conclude that the reduced HPA-reactivity during AT1-blockade could not be mimicked in a specific transgenic rat model featuring a centrally inactivated RAAS. The ACTH-independency of the enhanced corticosterone release during CRH-test and the enhanced corticosterone response to ACTH rather indicates an adrenal mechanism. The upregulation of adrenal MC2- and AT2-receptors seems to be involved in the stimulated facilitation of adrenal corticosterone release for effectuating the stimulated stress responses. |
| Keywords: | Adrenal Glands, Adrenocorticotropic Hormone, Angiotensin II, Angiotensinogen, Blood Pressure, Brain, Corticosterone, Corticotropin-Releasing Hormone, Hypothalamo-Hypophyseal System, Messenger RNA, Type 2 Angiotensin Receptor, Type 2 Melanocortin Receptor, Renin-Angiotensin System, Physiological Stress, Swimming, Up-Regulation, Animals, Rats |
| Source: | Journal of Endocrinology |
| ISSN: | 0022-0795 |
| Publisher: | BioScientifica |
| Volume: | 204 |
| Number: | 1 |
| Page Range: | 85-92 |
| Date: | January 2010 |
| Official Publication: | https://doi.org/10.1677/JOE-09-0363 |
| PubMed: | View item in PubMed |
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