Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD-containing peptide
D'Angelo, G.; Mogford, J.E.; Davis, G.E.; Davis, M.J.; Meininger, G.A.
American Journal of Physiology 272(4 Pt 2): H2065-H2070
1997
ISSN/ISBN: 0002-9513 PMID: 9139994 Document Number: 472575
It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha-v-beta-3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca-2+ concentration ((Ca-2+)-i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. (Ca-2+)-i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 mu-M) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, (Ca-2+)-i decreased from 91 +- 6 to 27 +- 4 nM (69.7 +- 5.0% reduction). In association with the decrease in (Ca-2+)-i, arteriolar lumen diameter increased from 89 +- 8 to 184 +- 8 mu (89.8 +- 1.8% dilation). At intermediate concentrations, cycloRGD induced rhythmic spiking of Ca-2+ superimposed on the concentration-dependent lowering of basal (Ca-2+)-i. These data directly link integrin activation with alterations in Ca-2+ regulation, the net effect of which is a reduction in (Ca-2+)-i. These data further suggest that integrins, through their role in mediating cellular attachment to the extracellular matrix and in cellular signaling involving Ca-2+, could provide a logical link to mechanotransduction and myogenic phenomena.