Nitric oxide effects on the function of aged cells ex vivo and in vivo

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.

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.

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.

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.