KATP-channel-induced vasodilation is modulated by the Na,K-pump activity in rabbit coronary small arteries.
The purpose of the study was to evaluate the importance of the Na,K-pump in relaxations induced by K(ATP)-channel openers in rabbit coronary small arteries. Arterial segments were mounted in myographs for recording of isometric tension. Whole-cell patch clamp was used to assess K(ATP)-channel currents in isolated smooth muscle cells from the arteries. In arteries preconstricted with the thromboxane A(2) analogue U46619 pinacidil and cromakalim induced concentration-dependent relaxations. In arteries preconstricted with potassium (124 mM) only high concentrations of pinacidil had a small relaxant effect. In arteries preconstricted with U46619 pinacidil-induced relaxations were unaffected by pretreatment with N(omega)-nitro-L-arginine (L-NNA) and only slightly reduced after mechanical removal of the endothelium. Pinacidil induced relaxations were not significantly affected by 1 microM glibenclamide. However, the relaxations were partly inhibited in potassium-free media and by 1 microM ouabain. In contrast, the concentration-dependent relaxation to cromakalim was partly blocked by 1 microM glibenclamide and partly by 1 microM ouabain and when both drugs were present the inhibition increased. Ouabain (1 microM) and glibenclamide (1 microM) each partly inhibited an ATP-sensitive current induced by pinacidil and cromakalim. In the presence of both inhibitors a greater inhibition was seen. When the solution in the patch pipette was sodium-free the current was reduced and ouabain had no effect. The study suggests that the relaxation to cromakalim and most likely pinacidil is mediated through opening of K(ATP) channels. Inhibition of the Na,K-pump, however, may change the local environment for the K(ATP) channels (i.e. increases the ATP/ADPratio and/or decreases the transmembrane potassium gradient), which partly prevents the activation of the K(ATP)-channel current.
Glavind-Kristensen
Marianne
M
Research Laboratory, Department of Obstetrics and Gynecology, Aarhus University Hospital, 8200 Aarhus, Denmark. mgk-njh@dadlnet.dk
Matchkov
Vladimir
V
Hansen
Vibeke Brogaard
VB
Forman
Axel
A
Nilsson
Holger
H
Aalkjaer
Christian
C
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019806:Cromakalim / Q000494:pharmacology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020110:Pinacidil / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D018528:ATP-Binding Cassette Transporters; D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D054086:KATP Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; C092520:uK-ATP-1 potassium channel; D019806:Cromakalim; D010042:Ouabain; D020110:Pinacidil; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D005905:Glyburide