A complete understanding of the biological mechanisms that take part i
n the hyperacute vascular rejection is necessary to prevent its develo
pment. Nitric Oxide (NO) release by the graft could be one of those me
chanisms as cytokine induction of NO synthase in reticuloendothelial c
ells produces NO with cytotoxic activity. We have performed 20 heterot
opic pig-to-dog kidney xenotransplantations in order to determine if c
ytotoxic NO is released during the hyperacute rejection. Nitrites and
cGMP levels were determined in plasma samples taken from the graft art
ery and vein until vessel thromboses. NO synthase activity was measure
d in pieces from renal artery and renal tissue. The results show that
after discordant xenotransplantation, inducible NO synthase is activat
ed in the transplanted organ, indicating that NO can mediate host tiss
ue damage during the hyperacute rejection. (C) 1996 Academic Press, In
c.