Role of endothelium in regulation of smooth muscle membrane potential and tone in the rabbit middle cerebral artery

The characteristic features of the endothelium‐mediated regulation of the electrical and mechanical activity of the smooth muscle cells of cerebral arteries were studied by measuring membrane potential and isometric force in endothelium‐intact and ‐denuded strips taken from the rabbit middle cerebral artery (MCA). In endothelium‐intact strips, histamine (His, 3–10 μM) and high K+ (20–80 mM) concentration‐dependently produced a transient contraction followed by a sustained contraction. Noradrenaline (10 μM), 5‐hydroxytryptamine (10 μM) and 9,11‐epithio‐11, 12‐methano‐thromboxane A2 (10 nM) each produced only a small contraction (less than 5% of the maximum K+‐induced contraction). NG‐nitro‐L‐arginine (L‐NOARG, 100 μM), but not indomethacin (10 μM), greatly enhanced the phasic and the tonic contractions induced by His (1–10 μM) in endothelium‐intact, but not in endothelium‐denuded strips, suggesting that spontaneous or basal release of nitric oxide (NO) from endothelial cells potently attenuates the His‐induced contractions. Acetylcholine (ACh, 0.3–3 μM) caused concentration‐dependent relaxation (maximum relaxation by 89.7±7.5%, n=4, P