| Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats. | |
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MedLine Citation:
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PMID: 20553918 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Acidosis modulates physiologic and pathophysiologic processes but the mechanism of acidotic vasodilatation remains unclear. We therefore explored this in aortic rings from normal and streptozotocin-induced diabetic Sprague-Dawley rats. Phenylephrine (PE)-induced contraction in endothelium-intact and -denuded rings were recorded under normal and acidotic pH with or without drug probes. Acidosis exerted a relaxant effect in endothelium-intact and -denuded euglycaemic and diabetic tissues. l-NAME or methylene blue partially inhibited acidotic relaxation in these endothelium-intact but not the -denuded tissues, with greater inhibition in the diabetic tissues, indicating that acidosis induces relaxation by endothelium-dependent and -independent mechanisms, the former being EDNO-cGMP mediated. Indomethacin had no effect on the tissues, indicating that cyclooxygenase products are neither involved in acidosis-induced vasodilatation nor in the modulation of phenylephrine-contraction. In euglycaemic tissues under normal pH, no K(+) channel blocker altered phenylephrine-contraction, but all (except glibenclamide) enhanced diabetic tissue contraction, indicating that normally, these channels (K(ir), K(V), BK(Ca), K(ATP)) do not modulate phenylephrine-contraction, but they (except K(ATP)) are expressed in diabetes where they attenuate phenylephine-induced contraction and modulate acidosis. Only the K(ir) channel modulates acidotic relaxation in euglycaemic tissues. Only tetraethylammonium and iberiotoxin enhanced phenylephrine-induced contraction in endothelium-denuded diabetic tissues indicating that BK(Ca) attenuates phenylephrine-contraction and that acidotic relaxation in this condition is modulated by a tetraethylammonium-sensitive mechanism. In conclusion, acidosis causes vasodilatation in normal and diabetic tissues via endothelium-dependent and -independent mechanisms differentially modulated by a combination of a NO-cGMP process and K(+) channels, some of which are dormant in the normal state but activated in diabetes mellitus. |
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Authors:
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Jian Loong Yeo; Boris Teng Chuan Tan; Francis I Achike |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-08 |
Journal Detail:
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Title: European journal of pharmacology Volume: 642 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-13 Completed Date: 2010-10-28 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 99-106 Citation Subset: IM |
Copyright Information:
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Copyright (c) 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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International Medical University, Commonwealth Plaza, Bukit Jalil, 57000 Kuala Lumpur, Malaysia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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4-Aminopyridine
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pharmacology Acidosis / physiopathology* Animals Aorta / drug effects, pathology*, physiopathology* Barium Compounds / pharmacology Chlorides / pharmacology Diabetes Mellitus / pathology, physiopathology* Endothelium, Vascular / drug effects, pathology*, physiopathology* Glucose Clamp Technique Glyburide / pharmacology Indomethacin / pharmacology Male Methylene Blue / pharmacology NG-Nitroarginine Methyl Ester / pharmacology Peptides / pharmacology Rats Rats, Sprague-Dawley Tetraethylammonium / pharmacology Vasodilation* / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Barium Compounds; 0/Chlorides; 0/Peptides; 10238-21-8/Glyburide; 10361-37-2/barium chloride; 129203-60-7/iberiotoxin; 504-24-5/4-Aminopyridine; 50903-99-6/NG-Nitroarginine Methyl Ester; 53-86-1/Indomethacin; 61-73-4/Methylene Blue; 66-40-0/Tetraethylammonium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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