The role of vascular myoglobin in nitrite-mediated blood vessel relaxation

Julian O M Ormerod, Houman Ashrafian, Abdul R Maher, Sayqa Arif, Violetta Steeples, Gustav V R Born, Stuart Egginton, Martin Feelisch, Hugh Watkins, Michael P Frenneaux

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Aims This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle—indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation.
Methods and results Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO.
Conclusion Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.
Original languageEnglish
Pages (from-to)560-565
Number of pages6
JournalCardiovascular Research
Volume89
Issue number3
Early online date1 Oct 2010
DOIs
Publication statusPublished - 15 Feb 2011

Fingerprint

Myoglobin
Nitrites
Blood Vessels
Vasodilation
Carbon Monoxide
Heme
Nitrite Reductases
Adenoviridae
Knockout Mice
Nitric Oxide
Proteins
Pharmacology

Keywords

  • vasodilation
  • nitrite
  • nitric oxide
  • myoglobin

Cite this

Ormerod, J. O. M., Ashrafian, H., Maher, A. R., Arif, S., Steeples, V., Born, G. V. R., ... Frenneaux, M. P. (2011). The role of vascular myoglobin in nitrite-mediated blood vessel relaxation. Cardiovascular Research, 89(3), 560-565. https://doi.org/10.1093/cvr/cvq299

The role of vascular myoglobin in nitrite-mediated blood vessel relaxation. / Ormerod, Julian O M; Ashrafian, Houman; Maher, Abdul R; Arif, Sayqa; Steeples, Violetta; Born, Gustav V R; Egginton, Stuart; Feelisch, Martin; Watkins, Hugh; Frenneaux, Michael P.

In: Cardiovascular Research, Vol. 89, No. 3, 15.02.2011, p. 560-565.

Research output: Contribution to journalArticle

Ormerod, JOM, Ashrafian, H, Maher, AR, Arif, S, Steeples, V, Born, GVR, Egginton, S, Feelisch, M, Watkins, H & Frenneaux, MP 2011, 'The role of vascular myoglobin in nitrite-mediated blood vessel relaxation', Cardiovascular Research, vol. 89, no. 3, pp. 560-565. https://doi.org/10.1093/cvr/cvq299
Ormerod JOM, Ashrafian H, Maher AR, Arif S, Steeples V, Born GVR et al. The role of vascular myoglobin in nitrite-mediated blood vessel relaxation. Cardiovascular Research. 2011 Feb 15;89(3):560-565. https://doi.org/10.1093/cvr/cvq299
Ormerod, Julian O M ; Ashrafian, Houman ; Maher, Abdul R ; Arif, Sayqa ; Steeples, Violetta ; Born, Gustav V R ; Egginton, Stuart ; Feelisch, Martin ; Watkins, Hugh ; Frenneaux, Michael P. / The role of vascular myoglobin in nitrite-mediated blood vessel relaxation. In: Cardiovascular Research. 2011 ; Vol. 89, No. 3. pp. 560-565.
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AB - Aims This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle—indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. Methods and results Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. Conclusion Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.

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