VASCULAR SMOOTH-MUSCLE ALPHA(V)BETA(3) INTEGRIN MEDIATES ARTERIOLAR VASODILATION IN RESPONSE TO RGD PEPTIDES

Arteriolar vasodilation and the resultant increase in blood flow are c haracteristic vascular responses to tissue injury. The dilatory mediat ors signaling these responses are incompletely understood. We show tha t integrin-binding peptides containing the Arg-Gly-Asp (RGD) tripeptid e sequence cause immediate and, in some instances, sustained vasodilat ion when applied to isolated rat cremaster arterioles. The vasodilatio n is dependent on interaction of the soluble RGD sequence with the alp ha(v) beta(3) integrin expressed by smooth muscle cells in the arterio lar wall. Possible in vivo sources of soluble RGD sequences are fragme nts of extracellular matrix proteins that are generated after tissue i njury. Indeed, protease-generated fragments of denatured collagen type I (a major source of RGD sequences) also cause cremaster arteriolar v asodilation through the alpha(v) beta(3) integrin. Thus, extracellular matrix protein fragments containing the RGD sequence may act as vascu lar wound recognition signals to regulate blood flow to injured tissue .