دورية أكاديمية
Improvement of endothelium-dependent vasodilations by SKA-31 and SKA-20, activators of small- and intermediate-conductance Ca2+ -activated K+ -channels.
العنوان: | Improvement of endothelium-dependent vasodilations by SKA-31 and SKA-20, activators of small- and intermediate-conductance Ca2+ -activated K+ -channels. |
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المؤلفون: | Hasenau AL; Faculty of Medicine, Philipps University, Marburg, Germany., Nielsen G, Morisseau C, Hammock BD, Wulff H, Köhler R |
المصدر: | Acta physiologica (Oxford, England) [Acta Physiol (Oxf)] 2011 Sep; Vol. 203 (1), pp. 117-26. Date of Electronic Publication: 2011 Mar 01. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101262545 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1748-1716 (Electronic) Linking ISSN: 17481708 NLM ISO Abbreviation: Acta Physiol (Oxf) Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Oxford : Wiley-Blackwell Original Publication: Oxford : Blackwell Pub., c2006-4 |
مواضيع طبية MeSH: | Benzothiazoles/*pharmacology , Endothelium, Vascular/*drug effects , Intermediate-Conductance Calcium-Activated Potassium Channels/*drug effects , Vasodilation/*drug effects, Animals ; Carotid Arteries/drug effects ; Carotid Arteries/metabolism ; Endothelium, Vascular/metabolism ; Mice ; Mice, Knockout ; Patch-Clamp Techniques ; Vasodilation/physiology |
مستخلص: | Aim: Endothelial membrane hyperpolarization mediated by KCa3.1 and KCa2.3 channels has been demonstrated to initiate endothelium-derived hyperpolarizing factor (EDHF)-type vasodilations. Moreover, pharmacological potentiation of KCa3.1/KCa2.3 channels has been suggested to improve EDHF-type vasodilations. Herein, we determined whether the KCa3.1/KCa2.3 activator SKA-31 and its derivative SKA-20 improve endothelial dysfunction in KCa3.1-/- and NOS3-/- mice. Methods: Membrane potentials were measured using patch-clamp electrophysiology on carotid artery (CA) endothelial cells (CAEC) from wild-type (wt) and KCa3.1-/- mice. Endothelium-dependent vasodilations were determined by pressure myography in CA. Results: SKA-31 (1 μm) activated KCa3.1 and KCa2.3 channels and induced membrane hyperpolarization in CAEC of wt (ΔMP -45 mV). These responses were significantly reduced in CAEC of KCa3.1-/- (ΔMP -8 mV). SKA-31 (200 nm, 500 nm) and SKA-20 (300 nm) significantly enhanced EDHF vasodilations in wt. SKA-20 also improved vasodilations during NO synthesis. In KCa3.1-/-, the defective EDHF vasodilations were unchanged at 200 nm SKA-31, but were significantly improved at 500 nm. EDHF vasodilations were slightly enhanced at 300 nm SKA-20, but vasodilations during NO synthesis were unchanged. SKA-31 (500 nm) enhanced the impaired endothelium-dependent vasodilation in NOS3-/- mice twofold. Pharmacological inhibition of the soluble epoxide hydrolase by t-AUCB (1 μm) in contrast did not increase ACh-induced EDHF- or NO-mediated vasodilations in wt and KCa3.1-/-. Conclusion: Normal and defective endothelium-dependent vasodilations in murine carotid arteries can be improved by pharmacological enhancement of KCa3.1/KCa2.3 functions. These findings further support the concept that pharmacological activation of endothelial KCa2.3/KCa3.1 could offer a novel endothelium-specific antihypertensive strategy. (© 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.) |
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معلومات مُعتمدة: | R21 NS052165 United States NS NINDS NIH HHS; R21 NS052165-02 United States NS NINDS NIH HHS; R21-NS052165 United States NS NINDS NIH HHS; R01 ES002710 United States ES NIEHS NIH HHS; R01 GM076063 United States GM NIGMS NIH HHS; R01 ES002710-31 United States ES NIEHS NIH HHS; R21 NS072585 United States NS NINDS NIH HHS |
المشرفين على المادة: | 0 (Benzothiazoles) 0 (Intermediate-Conductance Calcium-Activated Potassium Channels) 0 (Kcnn4 protein, mouse) 0 (naphtho(1,2-d)thiazol-2-ylamine) |
تواريخ الأحداث: | Date Created: 20110303 Date Completed: 20111207 Latest Revision: 20211020 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC3139805 |
DOI: | 10.1111/j.1748-1716.2010.02240.x |
PMID: | 21362152 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1748-1716 |
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DOI: | 10.1111/j.1748-1716.2010.02240.x |