Levcromakalim decreases cytoplasmic Ca2+ and vascular tone in basilar artery of SAH model dogs.
We investigated the effects of levcromakalim, a K+ channel opener, on [Ca2+]i and the contractile force of basilar arteries obtained from normal dogs and subarachnoid hemorrhage (SAH) dogs. The responsiveness to serotonin was increased more in the SAH group than in the control group. Levcromakalim decreased the resting [Ca2+]i and force more profoundly than did a Ca2+ channel blocker, nicardipine, and these effects were more prominent in the SAH group than in the control group. Levcromakalim diminished the increases in [Ca2+]i and contractile force induced by serotonin more profoundly than nicardipine did, and these effects were equal in both groups. The effects of levcromakalim were not inhibited by iberiotoxin but were antagonized completely by glibenclamide. These results suggest that levcromakalim-induced opening of adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channels reduces [Ca2+]i more effectively than does nicardipine and that levcromakalim exerts the vasodilator effects under the condition in which large conductance Ca2+-activated K+ (BK) channels are blocked with iberiotoxin. Consequently, K+ channel openers like levcromakalim may be useful drug candidates to treat delayed cerebral vasospasm after SAH.
Sugai
K
K
Department of Neurosurgery, Tohoku University School of Medicine, Sendai, Japan.
Yaganisawa
T
T
Motohashi
O
O
Suzuki
M
M
Yoshimoto
T
T
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D019806:Cromakalim / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism*; D004285:Dogs; D005260:Female; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015221:Potassium Channels / Q000819:agonists; D011897:Random Allocation; D013345:Subarachnoid Hemorrhage / Q000473:pathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; D002118:Calcium