An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress

Sarah Jane Smillie, Ross King, Xenia Kodji, Emilie Outzen, G. Pozsgai, Elizabeth Fernandes, Nichola Marshall, Patricia De Winter, Richard J. Heads, Cecile Dessapt-Baradez, Luigi Gnudi, Anette Sams, Ajay M. Shah, Richard C. Siow, Susan D. Brain

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms at the vascular level. Wild-type and αCGRP knockout mice that have similar baseline blood pressure were investigated in the angiotensin II hypertension model for 14 and 28 days. αCGRP knockout mice exhibited enhanced hypertension and aortic hypertrophy. αCGRP gene expression was increased in dorsal root ganglia and at the conduit and resistance vessel level of wild-type mice at both time points. βCGRP gene expression was also observed and shown to be linked to plasma levels of CGRP Mesenteric artery contractile and relaxant responses in vitro and endothelial NO synthase expression were similar in all groups. The aorta exhibited vascular hypertrophy, increased collagen formation, and oxidant stress markers in response to angiotensin II, with highest effects observed in αCGRP knockout mice. Gene and protein expression of endothelial NO synthase was lacking in the aortae after angiotensin II treatment, especially in αCGRP knockout mice. These results demonstrate the ongoing upregulation of αCGRP at the levels of both conduit and resistance vessels in vascular tissue in a model of hypertension and the direct association of this with protection against aortic vascular hypertrophy and fibrosis. This upregulation is maintained at a time when expression of aortic endothelial NO synthase and antioxidant defense genes have subsided, in keeping with the concept that the protective influence of αCGRP in hypertension may have been previously underestimated.

Original languageEnglish
Pages (from-to)1056-1062
Number of pages7
JournalHypertension
Volume63
Issue number5
DOIs
Publication statusPublished - 2014

Fingerprint

Calcitonin Gene-Related Peptide
Hypertrophy
Blood Vessels
Oxidative Stress
Hypertension
Knockout Mice
Angiotensin II
Nitric Oxide Synthase
Gene Expression
Aorta
Up-Regulation
Mesenteric Arteries
Spinal Ganglia
Vasodilator Agents
Oxidants
Fibrosis
Collagen
Antioxidants
Blood Pressure

Keywords

  • Angiotensin II
  • Calcitonin gene-related peptide
  • Hypertension
  • Hypertrophy
  • Mice
  • Nitric oxide
  • Oxidative stress

ASJC Scopus subject areas

  • Internal Medicine

Cite this

An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress. / Smillie, Sarah Jane; King, Ross; Kodji, Xenia; Outzen, Emilie; Pozsgai, G.; Fernandes, Elizabeth; Marshall, Nichola; De Winter, Patricia; Heads, Richard J.; Dessapt-Baradez, Cecile; Gnudi, Luigi; Sams, Anette; Shah, Ajay M.; Siow, Richard C.; Brain, Susan D.

In: Hypertension, Vol. 63, No. 5, 2014, p. 1056-1062.

Research output: Contribution to journalArticle

Smillie, SJ, King, R, Kodji, X, Outzen, E, Pozsgai, G, Fernandes, E, Marshall, N, De Winter, P, Heads, RJ, Dessapt-Baradez, C, Gnudi, L, Sams, A, Shah, AM, Siow, RC & Brain, SD 2014, 'An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress', Hypertension, vol. 63, no. 5, pp. 1056-1062. https://doi.org/10.1161/HYPERTENSIONAHA.113.02517
Smillie, Sarah Jane ; King, Ross ; Kodji, Xenia ; Outzen, Emilie ; Pozsgai, G. ; Fernandes, Elizabeth ; Marshall, Nichola ; De Winter, Patricia ; Heads, Richard J. ; Dessapt-Baradez, Cecile ; Gnudi, Luigi ; Sams, Anette ; Shah, Ajay M. ; Siow, Richard C. ; Brain, Susan D. / An ongoing role of α-calcitonin gene-related peptide as part of a protective network against hypertension, vascular hypertrophy, and oxidative stress. In: Hypertension. 2014 ; Vol. 63, No. 5. pp. 1056-1062.
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AU - Fernandes, Elizabeth

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AU - Heads, Richard J.

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AU - Sams, Anette

AU - Shah, Ajay M.

AU - Siow, Richard C.

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