Nitric Oxide Suppresses Cerebral Vasomotion by sGC-Independent Effects on Ryanodine Receptors and Voltage-Gated Calcium Channels

作者：Yuill Kathryn H; McNeish Alister J; Kansui Yasuo; Garland Christopher J; Dora Kim A^*

来源：Journal of Vascular Research, 2010, 47(2): 93-107.

DOI：10.1159/000235964

• Nitric oxide
• Membrane potential
• Calcium signalling
• Vascular smooth muscle
• Cerebral arteries
• Vasomotion

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 [Ca(2 )] ([Ca(2 )](SMC)) changes were recorded. Results: In the absence of L -NAME, asynchronous propagating Ca(2 ) waves were recorded that were sensitive to block with ryanodine, but not nifedipine. L -NAME stimulated pronounced vasomotion and synchronous Ca(2 ) oscillations with close temporal coupling between membrane potential, tone and [Ca(2 )](SMC). If nifedipine was applied together with L -NAME, [Ca(2 )] (SM)C decreased and synchronous Ca(2 ) oscillations were lost, but asynchronous propagating Ca(2 ) 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 BK(Ca) channels via ryanodine receptors (RYRs), with little involvement of sGC. Further, in whole cell mode, NO inhibited current through L-type voltage-gated Ca(2 ) 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.

• 出版日期2010