Journal article
Endothelium-dependent vasodilation in human mesenteric artery is primarily mediated by myoendothelial gap junctions intermediate conductance calcium-activated K+ channel and nitric oxide
Journal of Pharmacology and Experimental Therapeutics, Vol.336(3), pp.701-708
2011
Abstract
Myoendothelial microdomain signaling via localized calcium-activated potassium channel (KCa) and gap junction connexins (Cx) is critical for endothelium-dependent vasodilation in rat mesenteric artery. The present study determines the relative contribution of NO and gap junction-KCa mediated microdomain signaling to endothelium-dependent vasodilation in human mesenteric artery. The hypothesis tested was that such activity is due to NO and localized KCa and Cx activity. In mesenteric arteries from intestinal surgery patients, endothelium-dependent vasodilation was characterized using pressure myography with pharmacological intervention. Vessel morphology was examined using immunohistochemical and ultrastructural techniques. In vessel segments at 80 mm Hg, the intermediate (I)KCa blocker 1-[(2-chlorophenyl)diphenyl-methyl]-1H-pyrazole (TRAM-34; 1 μM) inhibited bradykinin (0.1 nM-3 μM)-induced vasodilation, whereas the small (S) KCa blocker apamin (50 and 100 nM) had no effect. Direct IK Ca activation with 1-ethyl-2-benzimidazolinone (1-EBIO; 10-300 μM) induced vasodilation, whereas cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6- methylpyrimidin-4-yl]-amine (1-30 μM), the SKCa activator, failed to dilate arteries, whereas dilation induced by 1-EBIO (10-100 μM) was blocked by TRAM-34. Bradykinin-mediated vasodilation was attenuated by putative gap junction block with carbenoxolone (100 μM), with remaining dilation blocked by N-nitro L-arginine methyl ester (100 μM) and [1H-[1,2,4] oxadiazolo-[4, 3-a]quinoxalin-1-one] (10 μM), NO synthase and soluble guanylate cyclase blockers, respectively. In human mesenteric artery, myoendothelial gap junction and IKCa activity are consistent with Cx37 and IKCa microdomain expression and distribution. Data suggest that endothelium-dependent vasodilation is primarily mediated by NO, IK Ca, and gap junction Cx37 in this vessel. Myoendothelial microdomain signaling sites are present in human mesenteric artery and are likely to contribute to endothelium-dependent vasodilation via a mechanism that is conserved between species.
Details
- Title
- Endothelium-dependent vasodilation in human mesenteric artery is primarily mediated by myoendothelial gap junctions intermediate conductance calcium-activated K+ channel and nitric oxide
- Authors
- P S Chadha (Author) - University of New South WalesLu Liu (Author) - University of New South WalesM Rikard-Bell (Author) - University of New South WalesS Senadheera (Author) - University of New South WalesL Howitt (Author) - University of New South WalesR L Bertrand (Author) - University of New South WalesT Hilton Grayson (Author) - University of New South WalesT V Murphy (Author) - University of New South WalesShaun L Sandow (Author) - University of New South Wales
- Publication details
- Journal of Pharmacology and Experimental Therapeutics, Vol.336(3), pp.701-708
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- Date published
- 2011
- DOI
- 10.1124/jpet.110.165795
- ISSN
- 0022-3565
- Organisation Unit
- School of Health - Biomedicine; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99449036902621
- Output Type
- Journal article
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