Conducted vascular responses: communication across the capillary bed

Conducted vasomotor responses are important for the effective distribution of blood flow, although the mechanism by which these responses are initiated is not well understood. ATP, a substance which is released from circulating red blood cells in response to low PO2 and low pH, two conditions which are associated with decreased supply relative to demand, has been shown to initiate conducted vasodilation following its intraluminal application in first and second order arterioles. Since such low PO2 and low pH conditions would most likely occur on the venous side of the vasculature, we evaluated the response of the arteriolar and capillary networks to application of ATP into venules in the Saran-covered hamster cheek pouch retractor muscle using in vivo video microscopy. Intraluminal application of 40 and 400 pl of 10(-6) M ATP resulted in dose-dependent increases in arteriolar diameter > 450 microm upstream from the site of application. These changes in arteriolar diameter were accompanied by significant increases in red blood cell flux. In capillaries, red blood cell flux doubled in response to ATP administration. Since NO was previously determined to be involved in the vascular response to intraluminal ATP in arterioles, we evaluated its role in these responses. We found that systemic administration of l-NAME prior to ATP application eliminated any conducted response and this effect of l-NAME was reversed by the systemic administration of l-arginine. These data suggest that ATP, which is released from red blood cells in response to low PO2 and low pH, conditions which would be found in the venular microvasculature, may serve a role in distributing perfusion in response to alterations in supply.