ILOPROST DILATES RAT SMALL ARTERIES - ROLE OF K-ATP-CHANNEL AND K-CA-CHANNEL ACTIVATION BY CAMP-DEPENDENT PROTEIN-KINASE

The effect of the stable prostacyclin analog iloprost and its mechanis m of action were investigated with the use of pressurized rat tail sma ll arteries with a spontaneous myogenic tone. Iloprost concentration d ependently dilated these vessels with a half-maximal effective dose of 5.0 +/- 0.5 x 10(-8) M. Application of 10(-7)-10(-6) M glibenclamide, a blocker of ATP-sensitive potassium (K-ATP) channels, inhibited the iloprost-induced dilation. Glibenclamide did not affect the basal vess el diameter. The application of 5 x 10(-5)-10(-3) M tetraethylammonium (TEA) and 5 x 10(-9)-10(-7) M iberiotoxin, blockers of calcium-activa ted potassium (Kc,) channels, decreased vessel diameter in the presenc e of iloprost. Both TEA and iberiotoxin reduced the basal vessel diame ter. Glibenclamide at 10(-6) M inhibited the dilation produced by 5 x 10(-5) M Sp-5,6-DCl-cBIMPS, an activator of adenosine 3',5'-cyclic mon ophosphate (cAMP)-dependent protein kinase. Iberiotoxin at 10(-7) M de creased vessel diameter in the presence of Sp-5,6-DCl-cBIMPS. H-89 and Rp-8-CPT-cAMPS, blockers of cAMP-dependent protein kinase A (PKA), in hibited the iloprost-induced dilation of these vessels. With use of th e whole cell configuration of the patch-clamp technique, it was observ ed that 5 x 10(-7) M iloprost enhanced an outward current, determined largely by Kc, channels, 1.79 +/- 0.17-fold in freshly isolated smooth muscle cells from rat tail small artery. These data show that ilopros t dilates rat tail small arteries with a spontaneous myogenic tone and suggest that K-ATP as well as Kc, channels are involved in this effec t, which is mediated, at least partly, by PKA.