Role of K+ channels in arteriolar vasodilation mediated by integrin interaction with RGD-containing peptide.
Integrins are transmembrane adhesion receptors found on most cells, including vascular smooth muscle cells. Several integrins bind to the conserved amino acid sequence Arg-Gly-Asp (RGD), and synthetic RGD-containing peptides can cause endothelium-independent arteriolar vasodilation by interacting with the alphavbeta3-integrin expressed by vascular smooth muscle. We hypothesized that RGD peptide-induced vasodilation involves K+ channels. Rat cremaster arterioles were treated with cRGD (GPenGRGDSPCA) in the presence or absence of the nonselective K+ channel inhibitor tetraethylammonium (TEA, 20 mM). TEA caused arterioles to constrict by 19 +/- 5% and inhibited cRGD-induced vasodilation (n = 7, P < 0.05). Vessels preconstricted with phenylephrine (5 x 10(-7) M) showed no significant inhibition of the dilatory response to cRGD, indicating that inhibition by TEA was not related to increased vasomotor tone. Further evidence for the involvement of K+ channels was obtained by addition of 100 mM KCl (n = 5), which inhibited vasodilation caused by cRGD. Inhibition of large and small conductance, Ca2+-activated K+ channels with iberiotoxin (100 nM) or apamin (25 nM), respectively, had no effect on cRGD-induced vasodilation. Partial inhibition of vasodilation was observed with inhibitors of voltage-gated (4-aminopyridine, 1 mM), ATP-sensitive (glibenclamide, 1 microM), and inward rectifying (barium, 50 microM) K+ channels. These data support the hypothesis that integrin-signaling pathways leading to arteriolar vasodilation may involve modulation of K+ channel function.
Platts
S H
SH
Microcirculation Research Institute, Department of Medical Physiology, Texas A & M University Health Science Center, College Station, Texas 77843-1114, USA.
Mogford
J E
JE
Davis
M J
MJ
Meininger
G A
GA
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D016023:Integrins / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
C085636:GpenGRGDSPCA; D016023:Integrins; D009842:Oligopeptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D011189:Potassium Chloride