Arteriolar responses to extracellular ATP in striated muscle

W. T. McCullough, D. M. Collins and M. L. Ellsworth Department of Pharmacological and Physiological Science, Saint Louis University Health Services Center, School of Medicine, Missouri 63104, USA. Blood flow and its distribution must be appropriately regulated to ensure that perfusion is matched to local tissue demands. We investigated the role of ATP in triggering a conducted alteration in arteriolar diameter in the Saran-covered cheek pouch retractor muscle of anesthetized hamsters (n = 60). Vascular responses were observed using in vivo video microscopy upstream from the site of micropressure application of ATP (10(-8)-10(-4) M) either into the lumen or just outside the wall of first- and second-order arterioles. The role of nitric oxide (NO) in the vascular responses to ATP was determined by inhibiting NO synthase activity with N(omega)-nitro-L-arginine methyl ester (L-NAME) with and without coadministration of an excess of L-arginine. Intraluminal application of ATP led to a concentration-dependent vasodilation, which was conducted upstream along the arteriole. The dilatory response was blocked by systemic pretreatment with L-NAME and was maintained in the presence of an excess of L-arginine. In contrast, ATP introduced extraluminally resulted in a conducted vasoconstrictor response that was enhanced by pretreatment with L-NAME. The dilator response to intraluminal ATP, in the context of ATP release from erythrocytes under conditions associated with decreased supply relative to demand, supports a role for the erythrocyte in communicating local tissue needs to the vasculature, enabling the appropriate matching of oxygen supply to demand.