Iloprost dilates rat small arteries: role of K(ATP)- and K(Ca)-channel activation by cAMP-dependent protein kinase
R. Schubert, V. N. Serebryakov, H. Mewes and H. H. Hopp Faculty of Medicine, University of Rostock, Germany. The effect of the stable prostacyclin analog iloprost and its mechanism of action were investigated with the use of pressurized rat tail small arteries with a spontaneous myogenic tone. Ilopr...
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Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 1997-03, Vol.272 (3), p.H1147-H1156 |
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Zusammenfassung: | R. Schubert, V. N. Serebryakov, H. Mewes and H. H. Hopp
Faculty of Medicine, University of Rostock, Germany.
The effect of the stable prostacyclin analog iloprost and its mechanism of
action were investigated with the use of pressurized rat tail small
arteries with a spontaneous myogenic tone. Iloprost concentration
dependently 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 vessel
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-activated
potassium (K(Ca)) channels, decreased vessel diameter in the presence of
iloprost. Both TEA and iberiotoxin reduced the basal vessel diameter.
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 monophosphate
(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 A (PKA), inhibited the
iloprost-induced dilation of these vessels. With use of the whole cell
configuration of the patch-clamp technique, it was observed that 5 x 10(-7)
M iloprost enhanced an outward current, determined largely by K(Ca)
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 with a spontaneous myogenic tone and suggest that K(ATP) as well
as K(Ca) channels are involved in this effect, which is mediated, at least
partly, by PKA. |
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ISSN: | 0363-6135 0002-9513 1522-1539 |
DOI: | 10.1152/ajpheart.1997.272.3.h1147 |