Integrin-binding peptides containing RGD produce coronary arteriolar dilation via cyclooxygenase activation

Integrin binding by Arg-Gly-Asp (RGD)-containing peptides has been shown to alter vascular tone in a variety of blood vessels and has been implicated as a mechanism of vasoregulation during tissue injury. However, the effect of these peptides in the coronary circulation has not been examined. Thus t he purpose of our study was to test the hypothesis that integrins act as re ceptors linked to the regulation of coronary vasomotor function. In particu lar, the ability of RGD-containing peptides to influence vascular tone by i nteracting with the alpha (v)beta (3)- and alpha (5)beta (1)- integrins was studied in isolated pig coronary arterioles. All vessels developed basal t one and dilated in a concentration-dependent manner to soluble peptides cyc lic GPenGRGDSPCA (cyclic RGD), an alpha (v)beta (3)-cyclic-binding peptide (XJ735), DMP7677, an alpha (5)beta (1)-binding peptide, and to protease-gen erated (neutrophil elastase) fragments of denatured collagen type I (a majo r RGD-containing extracellular matrix protein). The vasodilations to cyclic RGD, XJ735, and collagen fragments were almost completely blocked by endot helial removal or by the cyclooxygenase inhibitor indomethacin. In contrast , after endothelial removal and incubation with indomethacin, coronary arte rioles showed concentration-dependent constriction to the alpha (5)beta (1) -integrin ligand DMP7677 but not to cyclic RGD or XJ735. Collectively, our results indicate that activation of endothelial alpha (v)beta (3)- and alph a (5)beta (1)-integrins mediates coronary arteriolar dilation via the endot helial production of cyclooxygenase-derived prostaglandins. These data supp ort a role for integrins in the regulation of coronary vascular tone that m ay be particularly important during myocardial injury.