Background/Aims: In cerebral arteries, nitric oxide (NO) release plays a key role in suppressing vasomotion. Our aim was to establish the pathways affected by NO in rat middle cerebral arteries. Methods: In isolated segments of artery, isometric tension and simultaneous measurements of either smooth muscle membrane potential or intracellular [Ca2+] ([Ca2+]SMC) changes were recorded. Results: In the absence of L-NAME, asynchronous propagating Ca2+ waves were recorded that were sensitive to block with ryanodine, but not nifedipine. L-NAME stimulated pronounced vasomotion and synchronous Ca2+ oscillations with close temporal coupling between membrane potential, tone and [Ca2+]SMC. If nifedipine was applied together with L-NAME, [Ca2+]SMC decreased and synchronous Ca2+ oscillations were lost, but asynchronous propagating Ca2+ waves persisted. Vasomotion was similarly evoked by either iberiotoxin, or by ryanodine, and to a lesser extent by ODQ. Exogenous application of NONOate stimulated endothelium-independent hyperpolarization and relaxation of either L-NAME-induced or spontaneous arterial tone. NO-evoked hyperpolarization involved activation of BKCa channels via ryanodine receptors (RYRs), with little involvement of sGC. Further, in whole cell mode, NO inhibited current through L-type voltage-gated Ca2+ channels (VGCC), which was independent of both voltage and sGC. Conclusion: NO exerts sGC-independent actions at RYRs and at VGCC, both of which normally suppress cerebral artery myogenic tone.

Keywords:
Nitric oxide, Membrane potential, Calcium signalling, Vascular smooth muscle, Cerebral arteries, Vasomotion
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