Conducted vasomotor responses are important for the effective distribu
tion of blood flow, although the mechanism by which these responses ar
e initiated is not well understood. ATP, a substance which is released
from circulating red blood cells in response to low P-O2 and low pH,
two conditions which are associated with decreased supply relative to
demand, has been shown to initiate conducted vasodilation following it
s intraluminal application in first and second order arterioles. Since
such low P-O2 and low pH conditions would most likely occur on the ve
nous side of the vasculature, we evaluated the response of the arterio
lar and capillary networks to application of ATP into venules in the S
aran-covered hamster cheek pouch retractor muscle using in vivo video
microscopy. Intraluminal application of 40 and 400 pi of 10(-6) M ATP
resulted in dose-dependent increases in arteriolar diameter >450 mu m
upstream from the site of application. These changes in arteriolar dia
meter were accompanied by significant increases in red blood cell flux
. In capillaries, red blood cell flux doubled in response to ATP admin
istration. Since NO was previously determined to be involved in the va
scular response to intraluminal ATP in arterioles, we evaluated its ro
le in these responses. We found that systemic administration of L-NAME
prior to ATP application eliminated any conducted response and this e
ffect of L-NAME was reversed by the systemic administration of L-argin
ine. These data suggest that ATP, which is released from red blood cel
ls in response to low P-O2 and low pH, conditions which would be found
in the venular microvasculature, may serve a role in distributing per
fusion in response to alterations in supply. (C) 1998 Academic Press.