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. 2. Topical application of acetylcholine (10(-6) and 10(-5) M) increased diameter of the basilar artery from 238 +/- 7 microns to 268 +/- 7 and 288 +/- 7 microns, 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 microns to 246 +/- 7 and 261 +/- 7 microns, respectively. Thus, iberiotoxin attenuated acetylcholine-induced dilatation of the basilar artery (P < 0.05). 3. Sodium nitroprusside (10(-7) and 10(-6) M) increased diameter of the basilar artery from 242 +/- 9 microns to 310 +/- 12 and 374 +/- 13 microns, 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 microns to 259 +/- 9 and 311 +/- 12 microns, respectively. Thus, iberiotoxin attenuated dilator responses of the basilar artery to sodium nitroprusside (P < 0.05). 4. 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. 5. 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.
