title: Nitrite anion stimulates ischemic arteriogenesis involving NO metabolism.
abstract: Nitric oxide (NO) is a potential regulator of ischemic vascular remodeling, and as such therapies augmenting its bioavailability may be useful for the treatment of ischemic tissue diseases. Here we examine the effect of administering the NO prodrug sodium nitrite on arteriogenesis activity during established tissue ischemia. Chronic hindlimb ischemia was induced by permanent unilateral femoral artery and vein ligation. Five days postligation; animals were randomized to control PBS or sodium nitrite (165 μg/kg) therapy twice daily. In situ vascular remodeling was measured longitudinally using SPY angiography and Microfil vascular casting. Delayed sodium nitrite therapy rapidly increased ischemic limb arterial vessel diameter and branching in a NO-dependent manner. SPY imaging angiography over time showed that nitrite therapy enhanced ischemic gracillis collateral vessel formation from the profunda femoris to the saphenous artery. Immunofluorescent staining of smooth muscle cell actin also confirmed that sodium nitrite therapy increased arteriogenesis in a NO-dependent manner. The NO prodrug sodium nitrite significantly increases arteriogenesis and reperfusion of established severe chronic tissue ischemia.
authors.affiliation: Department of Pathology Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA 71130, USA.
authors.forename: Shyamal C
authors.initials: SC
authors.lastname: Bir
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Pattillo
authors.forename: Sibile
authors.initials: S
authors.lastname: Pardue
authors.forename: Gopi K
authors.initials: GK
authors.lastname: Kolluru
authors.forename: John
authors.initials: J
authors.lastname: Docherty
authors.forename: Dave
authors.initials: D
authors.lastname: Goyette
authors.forename: Peter
authors.initials: P
authors.lastname: Dvorsky
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kevil
mesh_terms: D000792:Angiography; D000818:Animals; D002908:Chronic Disease; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D005263:Femoral Artery / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D005268:Femoral Vein / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D011355:Prodrugs / Q000008:administration & dosage*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012720:Severity of Illness Index; D012977:Sodium Nitrite / Q000008:administration & dosage*
chemical_list: D020030:Nitric Oxide Donors; D011355:Prodrugs; D009569:Nitric Oxide; D012977:Sodium Nitrite