RGD-CONTAINING PEPTIDES INDUCE ENDOTHELIUM-DEPENDENT AND INDEPENDENT VASORELAXATIONS OF RAT AORTIC RINGS

Peptides containing the extracellular matrix peptide cell attachment s equence RGD possess potent, endothelium-dependent vasorelaxant propert ies. In the present study, the ability of RGD-containing peptides to c ause vasorelaxation in the presence and absence of a functional endoth elium was examined in rat aortic rings along with the ability of RGD-c ontaining peptides to increase cGMP production in these vessels. The a ctive RGD-containing peptide GRCDNP induced rapid relaxation in endoth elium-intact, norepinephrine contracted rat aortic rings. When the end othelium was removed, RGD-containing peptides produced a slow relaxati on of contracted rings which took approx. 40 min to reach maximum rela xation. Control RGD peptides were without effect either in the presenc e or absence of a functional endothelium. While acetylcholine and sodi um nitroprusside stimulated cGMP production in endothelium-intact and denuded aortic segments, neither the control RGD peptide nor the activ e GRGDNP increased cGMP in these vessels when compared to controls upo n either short (30 s) or long (45 min) incubation times. These data in dicate that relaxations of rat aortic rings in response to RGD-contain ing peptides occur both in the presence and absence of an intact endot helium and that cGMP is likely not the sole mediator of these response s.