Endothelium-derived hyperpolarizing factor but not NO reduces smooth muscle Ca2+ during acetylcholine-induced dilation of microvessels

Steffen Sebastian Bolz*, Cor De Wit, Ulrich Pohl

*Corresponding author for this work
88 Citations (Scopus)


1. We hypothesized that nitric oxide (NO) and the endothelium-dependent hyperpolarizing factor (EDHF) may dilate microvessels by different cellular mechanisms, namely Ca2+-desensitization versus decrease in intracellular free calcium. 2. Effects of acetylcholine (ACh) and the NO donors sodium nitroprusside (SNP, 0.1-10 μmol l-1) and S-Nitroso-N-acetyl-D,L-penicillamine (SNAP, 0.01-10 μmol l-1) on intracellular calcium ([Ca2+](i), fura 2) and vascular diameter (videomicroscopy) were studied in isolated resistance arteries from hamster gracilis muscle (194 ± 12 μm) pretreated with indomethacin and norepinephrine. Membrane potential changes were determined using 1,3-dibutylbarbituric acid trimethineoxonol (DiBAC4(3)). 3. ACh (0.1 and 1 μmol l-1)-induced dilations were associated with a [Ca2+](i) decrease (by 13 ± 3 and 32 ± 4%) and hyperpolarization of vascular smooth muscle (VSM, by 12 ± 1% at 1 μmol l-1 ACh). N(ω)-nitro-L-arginine (L-NA, 30 μmol l-1) partially inhibited the dilation but did not affect VSM [Ca2+](i) decreases or hyperpolarization. In contrast, the K(Ca) channel inhibitors tetrabutylammonium (TBA, 1 mmol l-1) and charybdotoxin (ChTX, 1 μmol l-1) abolished the ACh-induced [Ca2+](i) decrease and the hyperpolarization in VSM while a significant dilation remained (25 and 40%). This remaining dilation was abolished by L-NA. ChTX did not affect [Ca2+](i) increase and hyperpolarization in endothelial cells. SNP- or SNAP-induced dilations were not associated with decreases in VSM [Ca2+](i) or hyperpolarization although minor transient decreases in VSM [Ca2+](i) were observed at high concentrations. 4. These data suggest that ACh-induced dilations in microvessels are predominantly mediated by a factor different from NO and PGI2, presumably EDHF. EDHF exerts dilation by activation of K(Ca) channels and a subsequent decrease in VSM [Ca2+](i), NO dilates the microvessels in a calcium-independent manner.

Original languageEnglish
JournalBritish Journal of Pharmacology
Issue number1
Pages (from-to)124-134
Number of pages11
Publication statusPublished - 1999

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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