Flores, M., Graham, D. , Dominiczak, A. F. , Milligan, G. , Baker, A. H. and Nicklin, S. A. (2012) Abstract 231: angiotensin-(1-9) antagonises cardiac remodelling in a mouse model of Angiotensin Ii-induced hypertension. Hypertension, 60, A231.
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Publisher's URL: http://hyper.ahajournals.org/cgi/content/meeting_abstract/60/3_MeetingAbstracts/A231
Abstract
The identification of angiotensin converting enzyme-2 (ACE2), generating angiotensin-(1-7) [Ang-(1-7)] which signals via the Mas receptor to inhibit pathophysiological effects in cardiovascular disease has led to the definition of a counter-regulatory axis of the renin angiotensin system (RAS). Recently, we showed that another angiotensin peptide, Ang-(1-9), may also be part of this counter-regulatory axis as it prevents cardiomyocyte hypertrophy via the angiotensin type 2 receptor (AT2R). Furthermore, infusion of Ang-(1-9) via osmotic minipumps into stroke-prone spontaneously hypertensive rats reduced cardiac fibrosis via the AT2R. Here, we investigated Ang-(1-9) in an acute model of AngII-induced hypertension in C57BL/6J mice. Ang-(1-9), Ang-(1-9)+PD123,319 (AT2R antagonist), or water (control) were co-infused with AngII for 2 weeks via osmotic minipumps. Blood pressure was monitored via radiotelemetry. Significant increases in mean arterial pressure were observed in AngII infused mice compared to control (control 108.8±5.7 mmHg; AngII 125.1± 8.4 mmHg; p>0.05) however co-infusion of Ang-(1-9) or Ang-(1-9) and PD123,319 did not affect AngII-induced hypertension (AngII+ Ang-(1-9) 122.4±10.3 mmHg; AngII+Ang-(1-9)+PD123,319 118.3±mmHg; n=6 mice). When assessing cardiac hypertrophy by heart weight/tibia length ratio Ang-(1-9) reduced AngII-induced cardiac hypertrophy (ratio heart weight/tibia length: control 9.4 ± 1.2; AngII 11.9 ± 0.6; AngII+Ang-(1-9) 8.2 ± 0.7; p>0.01). Sections of heart were stained with wheat germ agglutinin and cardiomyocyte size measured supporting an anti-hypertrophic effect of Ang-(1-9) via the AT2R (control 25.7±3.8 μm; AngII 28.8±3.8 μm; AngII+Ang-(1-9) 24.6±4.8 μm; AngII+Ang-(1-9)+PD123,319 27.7±3.2μm; p>0.05). Furthermore, quantification of fibrosis following staining with picrosirius red also showed a significant reduction in animals co-infused with Ang-(1-9) and AngII compared to AngII-infusion (p>0.05). Further studies are ongoing to analyse cardiac effects of Ang-(1-9) at gene and protein level. These data support a direct biological role for Ang-(1-9) in cardiac remodeling and highlights Ang-(1-9) as a potential new therapeutic target in cardiovascular disease.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Baker, Professor Andrew and Graham, Dr Delyth and Flores, Dr Monica and Nicklin, Professor Stuart and Milligan, Professor Graeme and Dominiczak, Professor Anna |
| Authors: | Flores, M., Graham, D., Dominiczak, A. F., Milligan, G., Baker, A. H., and Nicklin, S. A. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Hypertension |
| Publisher: | American Heart Association |
| ISSN: | 0194-911X |
| ISSN (Online): | 1524-4563 |
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