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Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice.

Publication ,  Journal Article
Peña Silva, RA; Kung, DK; Mitchell, IJ; Alenina, N; Bader, M; Santos, RAS; Faraci, FM; Heistad, DD; Hasan, DM
Published in: Hypertension
August 2014

Angiotensin II (Ang II) stimulates vascular inflammation, oxidative stress, and formation and rupture of intracranial aneurysms in mice. Because Ang 1-7 acts on Mas receptors and generally counteracts deleterious effects of Ang II, we tested the hypothesis that Ang 1-7 attenuates formation and rupture of intracranial aneurysms. Intracranial aneurysms were induced in wild-type and Mas receptor-deficient mice using a combination of Ang II-induced hypertension and intracranial injection of elastase in the basal cistern. Mice received elastase+Ang II alone or a combination of elastase+Ang II+Ang 1-7. Aneurysm formation, prevalence of subarachnoid hemorrhage, mortality, and expression of molecules involved in vascular injury were assessed. Systolic blood pressure was similar in mice receiving elastase+Ang II (mean±SE, 148±5 mm Hg) or elastase+Ang II+Ang 1-7 (144±5 mm Hg). Aneurysm formation was also similar in mice receiving elastase+Ang II (89%) or elastase+Ang II+Ang 1-7 (84%). However, mice that received elastase+Ang II+Ang 1-7 had reduced mortality (from 64% to 36%; P<0.05) and prevalence of subarachnoid hemorrhage (from 75% to 48%; P<0.05). In cerebral arteries, expression of the inflammatory markers, Nox2 and catalase increased similarly in elastase+Ang II or elastase+Ang II+Ang 1-7 groups. Ang 1-7 increased the expression of cyclooxygenase-2 and decreased the expression of matrix metalloproteinase-9 induced by elastase+Ang II (P<0.05). In Mas receptor-deficient mice, systolic blood pressure, mortality, and prevalence of subarachnoid hemorrhage were similar (P>0.05) in groups treated with elastase+Ang II or elastase+Ang II+Ang 1-7. The expression of Mas receptor was detected by immunohistochemistry in samples of human intracranial arteries and aneurysms. In conclusion, without attenuating Ang II-induced hypertension, Ang 1-7 decreased mortality and rupture of intracranial aneurysms in mice through a Mas receptor-dependent pathway.

Duke Scholars

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Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

August 2014

Volume

64

Issue

2

Start / End Page

362 / 368

Location

United States

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins
  • Proto-Oncogene Mas
  • Peptide Fragments
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Intracranial Aneurysm
  • Humans
  • Cardiovascular System & Hematology
 

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Peña Silva, R. A., Kung, D. K., Mitchell, I. J., Alenina, N., Bader, M., Santos, R. A. S., … Hasan, D. M. (2014). Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice. Hypertension, 64(2), 362–368. https://doi.org/10.1161/HYPERTENSIONAHA.114.03415
Peña Silva, Ricardo A., David K. Kung, Ian J. Mitchell, Natalia Alenina, Michael Bader, Robson A. S. Santos, Frank M. Faraci, Donald D. Heistad, and David M. Hasan. “Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice.Hypertension 64, no. 2 (August 2014): 362–68. https://doi.org/10.1161/HYPERTENSIONAHA.114.03415.
Peña Silva RA, Kung DK, Mitchell IJ, Alenina N, Bader M, Santos RAS, et al. Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice. Hypertension. 2014 Aug;64(2):362–8.
Peña Silva, Ricardo A., et al. “Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice.Hypertension, vol. 64, no. 2, Aug. 2014, pp. 362–68. Pubmed, doi:10.1161/HYPERTENSIONAHA.114.03415.
Peña Silva RA, Kung DK, Mitchell IJ, Alenina N, Bader M, Santos RAS, Faraci FM, Heistad DD, Hasan DM. Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice. Hypertension. 2014 Aug;64(2):362–368.

Published In

Hypertension

DOI

EISSN

1524-4563

Publication Date

August 2014

Volume

64

Issue

2

Start / End Page

362 / 368

Location

United States

Related Subject Headings

  • Receptors, G-Protein-Coupled
  • Proto-Oncogene Proteins
  • Proto-Oncogene Mas
  • Peptide Fragments
  • Oxidative Stress
  • Mice, Knockout
  • Mice
  • Intracranial Aneurysm
  • Humans
  • Cardiovascular System & Hematology