Effects of sulfonylureas on K ATP channel-dependent vasodilation
Introduction: Sulfonylureas are widely prescribed for the treatment of type 2 diabetes. Their therapeutic efficacy resides in the ability to bind to sulfonylurea receptors (SURs) present on the β-cell plasma membrane, to close the ATP-regulated potassium (K ATP) channel, and thereby to enhance gluco...
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| Veröffentlicht in: | Journal of diabetes and its complications 2003-03, Vol.17 (2), p.6-10 |
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| creator | Cyrino, Fatima Z.G.A Bottino, Daniel A Coelho, Flavio C Ravel, Denis Bouskela, Eliete |
| description | Introduction: Sulfonylureas are widely prescribed for the treatment of type 2 diabetes. Their therapeutic efficacy resides in the ability to bind to sulfonylurea receptors (SURs) present on the β-cell plasma membrane, to close the ATP-regulated potassium (K
ATP) channel, and thereby to enhance glucose-stimulated insulin secretion. These receptors are also found in a wide variety of extra-pancreatic tissues such as brain, peripheral nerves, heart, and vascular smooth muscle where they contribute to the regulation of the vascular tone.
Objective: The objective of the present study was to determine the potency of three sulfonylureas, glibenclamide, gliclazide, and glimepiride, in antagonizing the vasorelaxant action of diazoxide, an ATP-regulated K
+ channel (K
ATP) opener, in vivo, using the hamster cheek pouch preparation and evaluating the changes in mean internal diameter and blood flow of arterioles and venules.
Material and methods: Cheek pouches of anesthetized male hamsters superfused with a HEPES-supported HCO
3
−-buffered saline solution were placed under an intravital microscope coupled to a closed-circuit TV system. All substances were applied topically.
Measurements: Mean arteriolar and venular internal diameters using an image shearing device, red blood cell (RBC) velocity by the dual-slit photometric technique and microvessel volume flow was calculated from diameters and RBC velocities.
Results: The numbers are given in order, first diameter and then flow, always for the highest concentration of diazoxide tested, by itself or in combination with a given sulfonylurea: (1) diazoxide, used in doses of 0.01, 1, and 100 μM, elicited a dose-dependent dilation and flow increase in arterioles [increase of 52.1% (
P |
| doi_str_mv | 10.1016/S1056-8727(02)00273-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_elsev</sourceid><recordid>TN_cdi_proquest_journals_1030093535</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1056872702002738</els_id><sourcerecordid>2718883691</sourcerecordid><originalsourceid>FETCH-LOGICAL-e169t-42a8ab15e443dac4f78efe0e02898d3d238f183a7bcc6de89b63017312dd39323</originalsourceid><addsrcrecordid>eNo1kE9LAzEQxYMoWKsfQVjwoofVSbKbzZ60lPoHCwpW8BbSZIJblqRudgv99qatMod5DI-ZNz9CLincUqDi7oNCKXJZseoa2A0Aq3guj8iIyiQKAV_HSf9bTslZjCsAEGVJR-Rh5hyaPmbBZXFoXfDbduhQp4HPXrPJ4j0z39p7bHOLa_QWfZ9tdAy2aXXfBH9OTpxuI1789TH5fJwtps_5_O3pZTqZ50hF3ecF01IvaYlFwa02haskOgQEJmtpuWVcOiq5rpbGCIuyXgoOtOKUWctrzviYXB32rrvwM2Ds1SoMnU8nFQUOUPMy1ZjcH1yYomwa7FQ0DXqDtunSm8qGJtnVDpvaY1M7JgqY2mNTkv8CWIFgFg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1030093535</pqid></control><display><type>article</type><title>Effects of sulfonylureas on K ATP channel-dependent vasodilation</title><source>Elsevier ScienceDirect Journals</source><creator>Cyrino, Fatima Z.G.A ; Bottino, Daniel A ; Coelho, Flavio C ; Ravel, Denis ; Bouskela, Eliete</creator><creatorcontrib>Cyrino, Fatima Z.G.A ; Bottino, Daniel A ; Coelho, Flavio C ; Ravel, Denis ; Bouskela, Eliete</creatorcontrib><description><![CDATA[Introduction: Sulfonylureas are widely prescribed for the treatment of type 2 diabetes. Their therapeutic efficacy resides in the ability to bind to sulfonylurea receptors (SURs) present on the β-cell plasma membrane, to close the ATP-regulated potassium (K
ATP) channel, and thereby to enhance glucose-stimulated insulin secretion. These receptors are also found in a wide variety of extra-pancreatic tissues such as brain, peripheral nerves, heart, and vascular smooth muscle where they contribute to the regulation of the vascular tone.
Objective: The objective of the present study was to determine the potency of three sulfonylureas, glibenclamide, gliclazide, and glimepiride, in antagonizing the vasorelaxant action of diazoxide, an ATP-regulated K
+ channel (K
ATP) opener, in vivo, using the hamster cheek pouch preparation and evaluating the changes in mean internal diameter and blood flow of arterioles and venules.
Material and methods: Cheek pouches of anesthetized male hamsters superfused with a HEPES-supported HCO
3
−-buffered saline solution were placed under an intravital microscope coupled to a closed-circuit TV system. All substances were applied topically.
Measurements: Mean arteriolar and venular internal diameters using an image shearing device, red blood cell (RBC) velocity by the dual-slit photometric technique and microvessel volume flow was calculated from diameters and RBC velocities.
Results: The numbers are given in order, first diameter and then flow, always for the highest concentration of diazoxide tested, by itself or in combination with a given sulfonylurea: (1) diazoxide, used in doses of 0.01, 1, and 100 μM, elicited a dose-dependent dilation and flow increase in arterioles [increase of 52.1% (
P<.01) and 41.2% (
P<.01)] and venules [37.9% (
P<.05) and 57.6% (
P<.01)]; (2) glibenclamide (0.81 μM)+diazoxide 29.3% (
P=.172) and 25.0% (
P=.064) for arterioles and 8% (
P=.654) and 3.7% (
P=.769) for venules; (3) gliclazide (12 μM)+diazoxide 51.0% (
P<.01) and 46.7% (
P<.01) for arterioles and 59.0% (
P<.01) and 45.2% (
P<.01) for venules; (4) glimepiride (0.82 μM)+diazoxide 22.8% (
P=.228) and 12.5% (
P=.305) for arterioles and 15.6% (
P=.415) and 16.0% (
P=.291) for venules.
Conclusion: These results suggest that, in contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide produce no cross-reactivity with smooth muscle cell K
ATP channels in the microvessels of the hamster cheek pouch. Previous studies have confirmed these results in isolated aortic rings of rats and guinea pigs.]]></description><identifier>ISSN: 1056-8727</identifier><identifier>EISSN: 1873-460X</identifier><identifier>DOI: 10.1016/S1056-8727(02)00273-8</identifier><language>eng</language><publisher>Philadelphia: Elsevier Inc</publisher><subject>ATP-regulated K + channel ; Blood ; Diazoxide ; Experiments ; Glibenclamide ; Gliclazide ; Glimepiride ; Hamster cheek pouch ; Microvascular reactivity ; Muscular system ; Rodents ; Smooth muscle ; Sulfonylureas ; Vasodilation</subject><ispartof>Journal of diabetes and its complications, 2003-03, Vol.17 (2), p.6-10</ispartof><rights>2003 Elsevier Science Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1056872702002738$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids></links><search><creatorcontrib>Cyrino, Fatima Z.G.A</creatorcontrib><creatorcontrib>Bottino, Daniel A</creatorcontrib><creatorcontrib>Coelho, Flavio C</creatorcontrib><creatorcontrib>Ravel, Denis</creatorcontrib><creatorcontrib>Bouskela, Eliete</creatorcontrib><title>Effects of sulfonylureas on K ATP channel-dependent vasodilation</title><title>Journal of diabetes and its complications</title><description><![CDATA[Introduction: Sulfonylureas are widely prescribed for the treatment of type 2 diabetes. Their therapeutic efficacy resides in the ability to bind to sulfonylurea receptors (SURs) present on the β-cell plasma membrane, to close the ATP-regulated potassium (K
ATP) channel, and thereby to enhance glucose-stimulated insulin secretion. These receptors are also found in a wide variety of extra-pancreatic tissues such as brain, peripheral nerves, heart, and vascular smooth muscle where they contribute to the regulation of the vascular tone.
Objective: The objective of the present study was to determine the potency of three sulfonylureas, glibenclamide, gliclazide, and glimepiride, in antagonizing the vasorelaxant action of diazoxide, an ATP-regulated K
+ channel (K
ATP) opener, in vivo, using the hamster cheek pouch preparation and evaluating the changes in mean internal diameter and blood flow of arterioles and venules.
Material and methods: Cheek pouches of anesthetized male hamsters superfused with a HEPES-supported HCO
3
−-buffered saline solution were placed under an intravital microscope coupled to a closed-circuit TV system. All substances were applied topically.
Measurements: Mean arteriolar and venular internal diameters using an image shearing device, red blood cell (RBC) velocity by the dual-slit photometric technique and microvessel volume flow was calculated from diameters and RBC velocities.
Results: The numbers are given in order, first diameter and then flow, always for the highest concentration of diazoxide tested, by itself or in combination with a given sulfonylurea: (1) diazoxide, used in doses of 0.01, 1, and 100 μM, elicited a dose-dependent dilation and flow increase in arterioles [increase of 52.1% (
P<.01) and 41.2% (
P<.01)] and venules [37.9% (
P<.05) and 57.6% (
P<.01)]; (2) glibenclamide (0.81 μM)+diazoxide 29.3% (
P=.172) and 25.0% (
P=.064) for arterioles and 8% (
P=.654) and 3.7% (
P=.769) for venules; (3) gliclazide (12 μM)+diazoxide 51.0% (
P<.01) and 46.7% (
P<.01) for arterioles and 59.0% (
P<.01) and 45.2% (
P<.01) for venules; (4) glimepiride (0.82 μM)+diazoxide 22.8% (
P=.228) and 12.5% (
P=.305) for arterioles and 15.6% (
P=.415) and 16.0% (
P=.291) for venules.
Conclusion: These results suggest that, in contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide produce no cross-reactivity with smooth muscle cell K
ATP channels in the microvessels of the hamster cheek pouch. Previous studies have confirmed these results in isolated aortic rings of rats and guinea pigs.]]></description><subject>ATP-regulated K + channel</subject><subject>Blood</subject><subject>Diazoxide</subject><subject>Experiments</subject><subject>Glibenclamide</subject><subject>Gliclazide</subject><subject>Glimepiride</subject><subject>Hamster cheek pouch</subject><subject>Microvascular reactivity</subject><subject>Muscular system</subject><subject>Rodents</subject><subject>Smooth muscle</subject><subject>Sulfonylureas</subject><subject>Vasodilation</subject><issn>1056-8727</issn><issn>1873-460X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNo1kE9LAzEQxYMoWKsfQVjwoofVSbKbzZ60lPoHCwpW8BbSZIJblqRudgv99qatMod5DI-ZNz9CLincUqDi7oNCKXJZseoa2A0Aq3guj8iIyiQKAV_HSf9bTslZjCsAEGVJR-Rh5hyaPmbBZXFoXfDbduhQp4HPXrPJ4j0z39p7bHOLa_QWfZ9tdAy2aXXfBH9OTpxuI1789TH5fJwtps_5_O3pZTqZ50hF3ecF01IvaYlFwa02haskOgQEJmtpuWVcOiq5rpbGCIuyXgoOtOKUWctrzviYXB32rrvwM2Ds1SoMnU8nFQUOUPMy1ZjcH1yYomwa7FQ0DXqDtunSm8qGJtnVDpvaY1M7JgqY2mNTkv8CWIFgFg</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>Cyrino, Fatima Z.G.A</creator><creator>Bottino, Daniel A</creator><creator>Coelho, Flavio C</creator><creator>Ravel, Denis</creator><creator>Bouskela, Eliete</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>ASE</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FPQ</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K6X</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope></search><sort><creationdate>20030301</creationdate><title>Effects of sulfonylureas on K ATP channel-dependent vasodilation</title><author>Cyrino, Fatima Z.G.A ; Bottino, Daniel A ; Coelho, Flavio C ; Ravel, Denis ; Bouskela, Eliete</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-e169t-42a8ab15e443dac4f78efe0e02898d3d238f183a7bcc6de89b63017312dd39323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>ATP-regulated K + channel</topic><topic>Blood</topic><topic>Diazoxide</topic><topic>Experiments</topic><topic>Glibenclamide</topic><topic>Gliclazide</topic><topic>Glimepiride</topic><topic>Hamster cheek pouch</topic><topic>Microvascular reactivity</topic><topic>Muscular system</topic><topic>Rodents</topic><topic>Smooth muscle</topic><topic>Sulfonylureas</topic><topic>Vasodilation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cyrino, Fatima Z.G.A</creatorcontrib><creatorcontrib>Bottino, Daniel A</creatorcontrib><creatorcontrib>Coelho, Flavio C</creatorcontrib><creatorcontrib>Ravel, Denis</creatorcontrib><creatorcontrib>Bouskela, Eliete</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>British Nursing Index</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>British Nursing Index</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><jtitle>Journal of diabetes and its complications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cyrino, Fatima Z.G.A</au><au>Bottino, Daniel A</au><au>Coelho, Flavio C</au><au>Ravel, Denis</au><au>Bouskela, Eliete</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of sulfonylureas on K ATP channel-dependent vasodilation</atitle><jtitle>Journal of diabetes and its complications</jtitle><date>2003-03-01</date><risdate>2003</risdate><volume>17</volume><issue>2</issue><spage>6</spage><epage>10</epage><pages>6-10</pages><issn>1056-8727</issn><eissn>1873-460X</eissn><abstract><![CDATA[Introduction: Sulfonylureas are widely prescribed for the treatment of type 2 diabetes. Their therapeutic efficacy resides in the ability to bind to sulfonylurea receptors (SURs) present on the β-cell plasma membrane, to close the ATP-regulated potassium (K
ATP) channel, and thereby to enhance glucose-stimulated insulin secretion. These receptors are also found in a wide variety of extra-pancreatic tissues such as brain, peripheral nerves, heart, and vascular smooth muscle where they contribute to the regulation of the vascular tone.
Objective: The objective of the present study was to determine the potency of three sulfonylureas, glibenclamide, gliclazide, and glimepiride, in antagonizing the vasorelaxant action of diazoxide, an ATP-regulated K
+ channel (K
ATP) opener, in vivo, using the hamster cheek pouch preparation and evaluating the changes in mean internal diameter and blood flow of arterioles and venules.
Material and methods: Cheek pouches of anesthetized male hamsters superfused with a HEPES-supported HCO
3
−-buffered saline solution were placed under an intravital microscope coupled to a closed-circuit TV system. All substances were applied topically.
Measurements: Mean arteriolar and venular internal diameters using an image shearing device, red blood cell (RBC) velocity by the dual-slit photometric technique and microvessel volume flow was calculated from diameters and RBC velocities.
Results: The numbers are given in order, first diameter and then flow, always for the highest concentration of diazoxide tested, by itself or in combination with a given sulfonylurea: (1) diazoxide, used in doses of 0.01, 1, and 100 μM, elicited a dose-dependent dilation and flow increase in arterioles [increase of 52.1% (
P<.01) and 41.2% (
P<.01)] and venules [37.9% (
P<.05) and 57.6% (
P<.01)]; (2) glibenclamide (0.81 μM)+diazoxide 29.3% (
P=.172) and 25.0% (
P=.064) for arterioles and 8% (
P=.654) and 3.7% (
P=.769) for venules; (3) gliclazide (12 μM)+diazoxide 51.0% (
P<.01) and 46.7% (
P<.01) for arterioles and 59.0% (
P<.01) and 45.2% (
P<.01) for venules; (4) glimepiride (0.82 μM)+diazoxide 22.8% (
P=.228) and 12.5% (
P=.305) for arterioles and 15.6% (
P=.415) and 16.0% (
P=.291) for venules.
Conclusion: These results suggest that, in contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide produce no cross-reactivity with smooth muscle cell K
ATP channels in the microvessels of the hamster cheek pouch. Previous studies have confirmed these results in isolated aortic rings of rats and guinea pigs.]]></abstract><cop>Philadelphia</cop><pub>Elsevier Inc</pub><doi>10.1016/S1056-8727(02)00273-8</doi><tpages>5</tpages></addata></record> |
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| issn | 1056-8727 1873-460X |
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| source | Elsevier ScienceDirect Journals |
| subjects | ATP-regulated K + channel Blood Diazoxide Experiments Glibenclamide Gliclazide Glimepiride Hamster cheek pouch Microvascular reactivity Muscular system Rodents Smooth muscle Sulfonylureas Vasodilation |
| title | Effects of sulfonylureas on K ATP channel-dependent vasodilation |
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