Iloprost dilates rat small arteries. role of katp- and kca-channel activation by camp-dependent protein kinase. Schubert, Rudolf, Vladimir N. Serebryakov*, Hartmut Mewes, and Hans -Heinrich Hopp. University of Rostock, Institute of Physiology, PSF 100888, D-18055 Rostock, Germany, Institute of Experimental Cardiology, Cardiology Research Center, Academy of Medical Sciences, 3rd Cherepkovskaya Street 15A, 121552 Moscow, Russia
APStracts 3:0448H, 1996.
The effect of the stable prostacyclin-analogue iloprost and its mechanism of action were investigated using pressurized rat tail small arteries possessing a spontaneous myogenic tone. Iloprost concentration-dependently dilated these vessels with an ED50 of 5.0+/-0.5x10-8 M. Application of 10-7-10-6 M glibenclamide, a blocker of ATP-sensitive potassium channels, inhibited the iloprost-induced dilation. Glibenclamide did not affect the basal vessel diameter. The application of 5x10-5-10-3 M TEA and 5x10-9-10-7 M iberiotoxin, blockers of calcium-activated potassium (KCa) channels, decreased vessel diameter in the presence of iloprost. TEA and iberiotoxin both reduced the basal vessel diameter. Glibenclamide at 10-6 M inhibited the dilation produced by 5x10-5 M Sp-5,6-DCl-cBIMPS, an activator of cAMP-dependent protein kinase. Iberiotoxin at 10-7 M decreased vessel diameter in the presence of Sp-5,6-DCl-cBIMPS. H-89 and Rp-8-CPT -cAMPS, blockers of cAMP-dependent protein kinase, inhibited the iloprost-induced dilation of these vessels. With use of the whole -cell configuration of the patch clamp technique, it was observed that 5x10-7 M iloprost enhanced an outward current, determined largely by KCa channels, 1.79+/-0.17-fold in freshly isolated smooth muscle cells from rat tail small artery. These data show that iloprost dilates rat tail small arteries possessing a spontaneous myogenic tone and suggest that ATP-sensitive as well as KCa channels are involved, an effect mediated, at least partly, by cAMP-dependent protein kinase. 

Received 27 November 1995; accepted in final form 9 October 1996.
APS Manuscript Number H1099-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996