INTEGRINS INHIBIT ANGIOTENSIN-II-INDUCED CONTRACTION IN RAT AORTIC RINGS

Many extracellular matrix proteins contain the tripeptide sequence arg inine-glycine-aspartate (RGD). This RGD motif is recognized by integri ns, a family of adhesion receptors present on vascular smooth muscle c ells. In the present study, we examined the ability of different RGD-c ontaining peptides to affect the contraction of rat aortic rings in re sponse to different agonists. We found that the peptide RGDS inhibited angiotensin-induced contraction in a dose dependent manner. In contra st, the peptides RGDW and RGES had no effect on angiotensin-induced co ntractility. We show that function-blocking antibodies to the integrin s alpha v beta 3 and alpha 5 beta 1 also inhibit angiotensin-induced c ontraction. These effects were observed in the absence of an intact en dothelium. In contrast, neither an antibody directed against the pi su bunit nor the peptide RGDS had an effect on phenylephrine or 5-hydroxy tryptamine-induced contraction. These data suggest that interactions o f vascular smooth muscle with components of the surrounding extracellu lar matrix may influence the response of smooth muscle to agonists. (C ) 1998 Elsevier Science B.V. All rights reserved.