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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1997 Jul;121(7):1315–1322. doi: 10.1038/sj.bjp.0701285

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

Nobutaka Yamakawa *,†,*, Masuo Ohhashi *, Shiro Waga , Takeo Itoh *
PMCID: PMC1564843  PMID: 9257909

Abstract

  1. 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).

  2. 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).

  3. 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<0.05) when applied to endothelium-intact strips precontracted with His. L-NOARG had little effect on this ACh-induced relaxation (n=4; P<0.05). Apamin (0.1 μM), but not glibenclamide (3 μM), abolished the relaxation induced by ACh (0.3–3 μM) in L-NOARG-treated strips (n=4, P<0.05).

  4. In endothelium-intact tissues, His (3 μM) depolarized the smooth muscle membrane potential (by 4.4±1.8 mV, n=12, P<0.05) whereas ACh (3 μM) caused membrane hyperpolarization (−20.9±3.0 mV, n=25, P<0.05). The ACh-induced membrane hypepolarization persisted after application of L-NOARG (−23.5±5.9 mV, n=8, P<0.05) or glibenclamide (−20.6±5.4 mV, n=5, P<0.05) but was greatly diminished by apamin (reduced to −5.8±3.2 mV, n=3, P<0.05).

  5. Sodium nitroprusside (0.1–10 μM) did not hyperpolarize the smooth muscle cell membrane potential (0.2±0.3 mV, n=4, P>0.05) but it greatly attenuated the His-induced contraction in endothelium-denuded strips (n=4, P<0.05).

  6. These results suggest that, under the present experimental conditions: (i) spontaneous or basal release of NO from endothelial cells exerts a significant negative effect on agonist-induced contractions in rabbit MCA, and (ii) ACh primarily activates the release of endothelium-derived hyperpolarizing factor (EDHF) in rabbit MCA.

Keywords: Endothelium-derived hyperpolarizing factor (EDHF), endothelium-derived relaxing factor (EDRF), acetylcholine, histamine, endothelium, cerebral vessels, smooth muscle physiology, smooth muscle pharmacology

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