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


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.


CONCLUSIONS
Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.
Ormerod
Julian O M
JO
Department of Cardiovascular Medicine, Birmingham University, Edgbaston, Birmingham, UK.
Ashrafian
Houman
H
Maher
Abdul R
AR
Arif
Sayqa
S
Steeples
Violetta
V
Born
Gustav V R
GV
Egginton
Stuart
S
Feelisch
Martin
M
Watkins
Hugh
H
Frenneaux
Michael P
MP
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009211:Myoglobin / Q000235:genetics* / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009572:Nitrite Reductases / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D009211:Myoglobin; D020030:Nitric Oxide Donors; D009573:Nitrites; D009599:Nitroprusside; D009569:Nitric Oxide; D002248:Carbon Monoxide; D009572:Nitrite Reductases