The role of potassium channels in relaxant effect of levosimendan in rat small mesenteric arteries.
We investigated both the effect of levosimendan and the role of various potassium channels in KCl-precontracted rat small mesenteric arteries. Levosimendan (10(-6)-10(-3) M) or cromakalim (CRO, 10(-7)-10(-4) M) produced concentration-dependent relaxation responses in small mesenteric arteries precontracted by 30 mM KCl. The relaxant responses to levosimendan in KCl-precontracted arteries did not differ significantly between endothelium-intact and endothelium-denuded preparations. Incubation of rat small mesenteric arterial segments with ATP-dependent potassium channel (KATP) blocker glibenclamide (GLI, 10(-6) M) for 30 min significantly inhibited the relaxant responses to both levosimendan and CRO. Neither the Ca(2+)-activated potassium channel (KCa) blocker iberiotoxin (10(-7) M) nor the voltage-dependent potassium channel (KV) blocker 4-aminopyridine (5 mM) incubation for 30 min caused significant alterations in relaxant responses to levosimendan in KCl-precontracted small mesenteric arteries. These findings suggested that levosimendan-induced relaxation responses in isolated rat small mesenteric arteries were neither depended on endothelium nor inhibited by the blockers of KV or KCa but, they rather seem to depend on the activation of KATP.
Department of Pharmacology, Akdeniz University, Medical Faculty, Antalya, Turkey. sozdem@akdeniz.edu.tr
Sadi S
SS
Ozdem
Ozlem
O
Yalcin
Herbert J
HJ
Meiselman
Oguz K
OK
Baskurt
Coskun
C
Usta
D000818:Animals; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000077464:Simendan; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D006835:Hydrazones; D024661:Potassium Channels, Inwardly Rectifying; D011724:Pyridazines; D014665:Vasodilator Agents; D019806:Cromakalim; D000077464:Simendan; D011189:Potassium Chloride; D005905:Glyburide