Endothelium-Dependent Vasodilation in Human Mesenteric Artery Is Primarily Mediated by Myoendothelial Gap Junctions Intermediate Conductance Calcium-Activated K+ Channel and Nitric Oxide
| Autor: | Preet S. Chadha, Shaun L. Sandow, Timothy V. Murphy, Rebecca L. Bertrand, Lauren Howitt, T. Hilton Grayson, Lu Liu, Sevvandi Senadheera, Matt Rikard-Bell |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Carbenoxolone Bradykinin Vasodilation Nitric Oxide Apamin Connexins Nitric oxide chemistry.chemical_compound medicine Humans Mesenteric arteries Endothelium-Dependent Relaxing Factors Pharmacology Gap junction Gap Junctions Anatomy Middle Aged Intermediate-Conductance Calcium-Activated Potassium Channels Potassium channel Mesenteric Arteries medicine.anatomical_structure chemistry Biophysics Molecular Medicine Female medicine.drug |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 336:701-708 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.110.165795 |
| Popis: | Myoendothelial microdomain signaling via localized calcium-activated potassium channel (K(Ca)) 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-K(Ca) mediated microdomain signaling to endothelium-dependent vasodilation in human mesenteric artery. The hypothesis tested was that such activity is due to NO and localized K(Ca) 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)K(Ca) 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) K(Ca) 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-methyl-pyrimidin-4-yl]-amine (1-30 μM), the SK(Ca) 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 IK(Ca) activity are consistent with Cx37 and IK(Ca) 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. |
| Databáze: | OpenAIRE |
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