Nitric oxide effects on the function of aged cells ex vivo and in vivo.
BACKGROUND
Angiogenesis is impaired in most aged tissues. Accordingly, there is great interest in interventions that improve the ability of aged cells to undergo blood vessel formation and subsequent tissue repair.


METHODS
Nitric oxide (NO), a mediator proposed to enhance angiogenesis, was administered (as the precursor SNAP, S-nitroso-N-acetylpenicillamine) to aortic ring explants from aged mice and to aged mice in two separate in vivo experiments: a PVA sponge implant model of angiogenesis and full thickness excisional dermal wounds.


RESULTS
SNAP inhibited angiogenesis from the mouse aortic ring explants. However, there was a trend toward increased blood vessel formation in the sponges from the aged mice treated with SNAP. SNAP did not detectably enhance dermal wound healing or angiogenesis, but it significantly inhibited epidermal closure.


CONCLUSIONS
These data underscore the complexity of using a single agent, even one with multiple mechanisms such as NO, to improve a clinical outcome such as angiogenesis or wound repair in aged animals.
Reed
May J
MJ
Department of Medicine, University of Washington, Harborview Medical Center, Seattle, WA 98104, USA. mjr@u.washington.edu
Eyman
Daniel
D
Karres
Nathan
N
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology* / Q000627:therapeutic use; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology* / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000293:injuries; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000503:physiopathology
D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine