Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats
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...
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| Veröffentlicht in: | European journal of pharmacology 2010-09, Vol.642 (1), p.99-106 |
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| description | 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. |
| doi_str_mv | 10.1016/j.ejphar.2010.05.040 |
| format | Article |
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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.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2010.05.040</identifier><identifier>PMID: 20553918</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>4-Aminopyridine - pharmacology ; Acidosis ; Acidosis - physiopathology ; Animals ; Aorta - drug effects ; Aorta - pathology ; Aorta - physiopathology ; Barium Compounds - pharmacology ; Biological and medical sciences ; Chlorides - pharmacology ; Diabetes mellitus ; Diabetes Mellitus - pathology ; Diabetes Mellitus - physiopathology ; Diabetes. Impaired glucose tolerance ; EDRF ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - pathology ; Endothelium, Vascular - physiopathology ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Glucose Clamp Technique ; Glyburide - pharmacology ; Indomethacin - pharmacology ; Male ; Medical sciences ; Methylene Blue - pharmacology ; NG-Nitroarginine Methyl Ester - pharmacology ; Peptides - pharmacology ; Pharmacology. Drug treatments ; Potassium channels ; Rats ; Rats, Sprague-Dawley ; Tetraethylammonium - pharmacology ; Vasodilation - drug effects</subject><ispartof>European journal of pharmacology, 2010-09, Vol.642 (1), p.99-106</ispartof><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright (c) 2010 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-f7077334e3f69296146f9c4131f5a4ed872f68df87e966246ac24dccfe9daf613</citedby><cites>FETCH-LOGICAL-c391t-f7077334e3f69296146f9c4131f5a4ed872f68df87e966246ac24dccfe9daf613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2010.05.040$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23025539$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20553918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yeo, Jian Loong</creatorcontrib><creatorcontrib>Tan, Boris Teng Chuan</creatorcontrib><creatorcontrib>Achike, Francis I.</creatorcontrib><title>Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>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.</description><subject>4-Aminopyridine - pharmacology</subject><subject>Acidosis</subject><subject>Acidosis - physiopathology</subject><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - pathology</subject><subject>Aorta - physiopathology</subject><subject>Barium Compounds - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Chlorides - pharmacology</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - pathology</subject><subject>Diabetes Mellitus - physiopathology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>EDRF</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - pathology</subject><subject>Endothelium, Vascular - physiopathology</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Glucose Clamp Technique</subject><subject>Glyburide - pharmacology</subject><subject>Indomethacin - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Methylene Blue - pharmacology</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Peptides - pharmacology</subject><subject>Pharmacology. Drug treatments</subject><subject>Potassium channels</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Tetraethylammonium - pharmacology</subject><subject>Vasodilation - drug effects</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM2OFCEURonROO3oGxjDxriqFiiKKjYmZjL-JJO40TW5AxebThW0QHecB_C9pdKt7lxxc3O-y5dDyEvOtpxx9Xa_xf1hB3krWFuxYcske0Q2fBp1x0YuHpMNY1x2Qmt9RZ6VsmeMDVoMT8mVYMPQaz5tyK_bn4c55RC_07pDuqDdQQxloclTjC615RxgpiGe0nzCBWNtMwUbXCqhdCG6o0VHT1CSCzNUqCHFNQ0p12BpDaUcsVCf00Jjyks7BtFRF-AeVyBDLc_JEw9zwReX95p8-3D79eZTd_fl4-eb93edbW1r50c2jn0vsfdKC624VF5byXvuB5DoplF4NTk_jaiVElKBFdJZ61E78Ir31-TN-e4hpx-tVTVLKBbnGSKmYzHtuJ7kNMhGyjNpcyolozeHHBbID4Yzs_o3e3P2b1b_hg2m-W-xV5cPjvcLur-hP8Ib8PoCQLEw-wzRhvKP65lYyca9O3PYdJwCZlNswNhUh4y2GpfC_5v8BhWCqG8</recordid><startdate>20100910</startdate><enddate>20100910</enddate><creator>Yeo, Jian Loong</creator><creator>Tan, Boris Teng Chuan</creator><creator>Achike, Francis I.</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100910</creationdate><title>Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats</title><author>Yeo, Jian Loong ; Tan, Boris Teng Chuan ; Achike, Francis I.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-f7077334e3f69296146f9c4131f5a4ed872f68df87e966246ac24dccfe9daf613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>4-Aminopyridine - pharmacology</topic><topic>Acidosis</topic><topic>Acidosis - physiopathology</topic><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - pathology</topic><topic>Aorta - physiopathology</topic><topic>Barium Compounds - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Chlorides - pharmacology</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - pathology</topic><topic>Diabetes Mellitus - physiopathology</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>EDRF</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - pathology</topic><topic>Endothelium, Vascular - physiopathology</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Glucose Clamp Technique</topic><topic>Glyburide - pharmacology</topic><topic>Indomethacin - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Methylene Blue - pharmacology</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>Peptides - pharmacology</topic><topic>Pharmacology. Drug treatments</topic><topic>Potassium channels</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Tetraethylammonium - pharmacology</topic><topic>Vasodilation - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yeo, Jian Loong</creatorcontrib><creatorcontrib>Tan, Boris Teng Chuan</creatorcontrib><creatorcontrib>Achike, Francis I.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yeo, Jian Loong</au><au>Tan, Boris Teng Chuan</au><au>Achike, Francis I.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2010-09-10</date><risdate>2010</risdate><volume>642</volume><issue>1</issue><spage>99</spage><epage>106</epage><pages>99-106</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>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.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20553918</pmid><doi>10.1016/j.ejphar.2010.05.040</doi><tpages>8</tpages></addata></record> |
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| subjects | 4-Aminopyridine - pharmacology Acidosis Acidosis - physiopathology Animals Aorta - drug effects Aorta - pathology Aorta - physiopathology Barium Compounds - pharmacology Biological and medical sciences Chlorides - pharmacology Diabetes mellitus Diabetes Mellitus - pathology Diabetes Mellitus - physiopathology Diabetes. Impaired glucose tolerance EDRF Endocrine pancreas. Apud cells (diseases) Endocrinopathies Endothelium, Vascular - drug effects Endothelium, Vascular - pathology Endothelium, Vascular - physiopathology Etiopathogenesis. Screening. Investigations. Target tissue resistance Glucose Clamp Technique Glyburide - pharmacology Indomethacin - pharmacology Male Medical sciences Methylene Blue - pharmacology NG-Nitroarginine Methyl Ester - pharmacology Peptides - pharmacology Pharmacology. Drug treatments Potassium channels Rats Rats, Sprague-Dawley Tetraethylammonium - pharmacology Vasodilation - drug effects |
| title | Exploring the mechanism of endothelial involvement in acidosis-induced vasodilatation of aortic tissues from normal and diabetic rats |
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