Role of Ca 2+ ‐activated K + channels in acetylcholine‐induced dilatation of the basilar artery in vivo

We tested the hypothesis that activation of large conductance calcium‐activated potassium channels is involved in dilator responses of the basilar artery to acetylcholine in vivo . Using a cranial window in anaesthetized rats, we examined responses of the basilar artery to acetylcholine. Topical application of acetylcholine (10 −6 and 10 −5 m ) increased diameter of the basilar artery from 238±7 μm to 268±7 and 288±7 μm, respectively ( P <0.05 vs. baseline diameter). Iberiotoxin (10 −8 m ), an inhibitor of large conductance calcium‐activated potassium channels, did not affect baseline diameter of the basilar artery. In the presence of 10 −8 m iberiotoxin, 10 −6 and 10 −5 m acetylcholine increased diameter of the basilar artery from 239±7 μm to 246±7 and 261±7 μm, respectively. Thus, iberiotoxin attenuated acetylcholine‐induced dilatation of the basilar artery ( P <0.05). Sodium nitroprusside (10 −7 and 10 −6 m ) increased diameter of the basilar artery from 242±9 μm to 310±12 and 374±13 μm, respectively ( P <0.05 vs. baseline diameter). In the presence of iberiotoxin (10 −8 m ), sodium nitroprusside (10 −7 and 10 −6 m ) increased diameter of the basilar artery from 243±6 μm to 259±9 and 311±12 μm, respectively. Thus, iberiotoxin attenuated dilator responses of the basilar artery to sodium nitroprusside ( P <0.05). Iberiotoxin partly inhibited dilator responses of the basilar artery to forskolin, a direct activator of adenylate cyclase, but did not affect vasodilatation produced by levcromakalim, a potassium channel opener. These results suggest that dilator responses of the basilar artery to acetylcholine and sodium nitroprusside are mediated, in part, by activation of large conductance calcium‐activated potassium channels. Because both acetylcholine and sodium nitroprusside have been shown to activate guanylate cyclase via nitric oxide, activation of large conductance calcium‐activated potassium channels may be one of the major mechanisms by which cyclic GMP causes dilatation of the basilar artery in vivo .British Journal of Pharmacology (1997) 120 , 102–106; doi: 10.1038/sj.bjp.0700880