Integrins inhibit angiotensin II-induced contraction in rat aortic rings.
Many extracellular matrix proteins contain the tripeptide sequence arginine-glycine-aspartate (RGD). This RGD motif is recognized by integrins, a family of adhesion receptors present on vascular smooth muscle cells. In the present study, we examined the ability of different RGD-containing peptides to affect the contraction of rat aortic rings in response to different agonists. We found that the peptide RGDS inhibited angiotensin-induced contraction in a dose dependent manner. In contrast, the peptides RGDW and RGES had no effect on angiotensin-induced contractility. We show that function-blocking antibodies to the integrins alphavbeta3 and alpha5beta1 also inhibit angiotensin-induced contraction. These effects were observed in the absence of an intact endothelium. In contrast, neither an antibody directed against the beta1 subunit nor the peptide RGDS had an effect on phenylephrine or 5-hydroxytryptamine-induced contraction. These data suggest that interactions of vascular smooth muscle with components of the surrounding extracellular matrix may influence the response of smooth muscle to agonists.
Schnapp
L M
LM
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. lschnapp@smtplink.mssm.edu
Goswami
S
S
Rienzi
N
N
Koteliansky
V E
VE
Gotwals
P
P
Schachter
E N
EN
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects*; D005109:Extracellular Matrix / Q000737:chemistry; D016023:Integrins / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017469:Receptors, Fibronectin / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology
D000906:Antibodies; D016023:Integrins; D009842:Oligopeptides; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D000804:Angiotensin II; D010656:Phenylephrine; D012701:Serotonin; C047981:arginyl-glycyl-aspartic acid; C059453:RGES peptide; C046617:arginyl-glycyl-aspartyl-serine