Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules
ABSTRACT Objective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes. Methods: The mesenteric microvasculature of rats was perfuse...
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| Veröffentlicht in: | Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2003-10, Vol.10 (5), p.411-420 |
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| creator | VALESKI, J. EDWARD BALDWIN, ANN L. |
| description | ABSTRACT
Objective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes.
Methods: The mesenteric microvasculature of rats was perfused with a fluorescent tracer plus thrombin, histamine, or buffered saline, and the preparation was suffused with the MLCK inhibitor ML‐7. The microvasculature then was stained for actin.
Results: The average (±SE) number of leaks per micrometer of venule length of the thrombin plus 5 µM ML‐7 treatment (35.3 ± 5.9 × 10−4; n = 224) was significantly lower than that for the thrombin‐only treatment (61.7 ± 5.6 × 10−4; n = 385; p < 0.001). The histamine preparations required higher concentrations of ML‐7 to significantly reduce the number of leaks. A concentration of 100 µM reduced the average leak number from 20.8 ± 3.9 × 10 4 (n = 140) to 2.5 ± 0.8 × 10−4 (n = 383; p < 0.001), but 20 µM ML‐7 had no effect. Although leaky areas of both the thrombin‐ and histamine‐treated preparations showed disruptions of the peripheral actin rim coincident with fluorescein isothiocyanate‐bovine serum albumin leaks, qualitative and quantitative differences were identified.
Conclusions: The results suggest both similar and dissimilar mechanisms for thrombin and histamine regarding in situ endothelial gap formation. |
| doi_str_mv | 10.1038/sj.mn.7800202 |
| format | Article |
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Objective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes.
Methods: The mesenteric microvasculature of rats was perfused with a fluorescent tracer plus thrombin, histamine, or buffered saline, and the preparation was suffused with the MLCK inhibitor ML‐7. The microvasculature then was stained for actin.
Results: The average (±SE) number of leaks per micrometer of venule length of the thrombin plus 5 µM ML‐7 treatment (35.3 ± 5.9 × 10−4; n = 224) was significantly lower than that for the thrombin‐only treatment (61.7 ± 5.6 × 10−4; n = 385; p < 0.001). The histamine preparations required higher concentrations of ML‐7 to significantly reduce the number of leaks. A concentration of 100 µM reduced the average leak number from 20.8 ± 3.9 × 10 4 (n = 140) to 2.5 ± 0.8 × 10−4 (n = 383; p < 0.001), but 20 µM ML‐7 had no effect. Although leaky areas of both the thrombin‐ and histamine‐treated preparations showed disruptions of the peripheral actin rim coincident with fluorescein isothiocyanate‐bovine serum albumin leaks, qualitative and quantitative differences were identified.
Conclusions: The results suggest both similar and dissimilar mechanisms for thrombin and histamine regarding in situ endothelial gap formation.</description><identifier>ISSN: 1073-9688</identifier><identifier>EISSN: 1549-8719</identifier><identifier>DOI: 10.1038/sj.mn.7800202</identifier><identifier>PMID: 14557824</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>actin cytoskeleton ; Actins - physiology ; Animals ; Azepines - pharmacology ; Capillary Permeability - drug effects ; Capillary Permeability - physiology ; Cytoskeleton - drug effects ; Cytoskeleton - physiology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - physiology ; Enzyme Inhibitors - pharmacology ; histamine ; Histamine - pharmacology ; Male ; Mesenteric Veins - drug effects ; Mesenteric Veins - physiology ; Microscopy, Fluorescence ; myosin light chain kinase ; Myosin-Light-Chain Kinase - antagonists & inhibitors ; Naphthalenes - pharmacology ; rat mesentery ; Rats ; Rats, Sprague-Dawley ; thrombin ; Thrombin - pharmacology ; venular permeability ; Venules - drug effects ; Venules - physiology</subject><ispartof>Microcirculation (New York, N.Y. 1994), 2003-10, Vol.10 (5), p.411-420</ispartof><rights>2003 Blackwell</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3696-47849b68541418e12190522b88aca941f922f72b137e4f16820380d8175af5763</citedby><cites>FETCH-LOGICAL-c3696-47849b68541418e12190522b88aca941f922f72b137e4f16820380d8175af5763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Fsj.mn.7800202$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Fsj.mn.7800202$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14557824$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>VALESKI, J. EDWARD</creatorcontrib><creatorcontrib>BALDWIN, ANN L.</creatorcontrib><title>Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules</title><title>Microcirculation (New York, N.Y. 1994)</title><addtitle>Microcirculation</addtitle><description>ABSTRACT
Objective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes.
Methods: The mesenteric microvasculature of rats was perfused with a fluorescent tracer plus thrombin, histamine, or buffered saline, and the preparation was suffused with the MLCK inhibitor ML‐7. The microvasculature then was stained for actin.
Results: The average (±SE) number of leaks per micrometer of venule length of the thrombin plus 5 µM ML‐7 treatment (35.3 ± 5.9 × 10−4; n = 224) was significantly lower than that for the thrombin‐only treatment (61.7 ± 5.6 × 10−4; n = 385; p < 0.001). The histamine preparations required higher concentrations of ML‐7 to significantly reduce the number of leaks. A concentration of 100 µM reduced the average leak number from 20.8 ± 3.9 × 10 4 (n = 140) to 2.5 ± 0.8 × 10−4 (n = 383; p < 0.001), but 20 µM ML‐7 had no effect. Although leaky areas of both the thrombin‐ and histamine‐treated preparations showed disruptions of the peripheral actin rim coincident with fluorescein isothiocyanate‐bovine serum albumin leaks, qualitative and quantitative differences were identified.
Conclusions: The results suggest both similar and dissimilar mechanisms for thrombin and histamine regarding in situ endothelial gap formation.</description><subject>actin cytoskeleton</subject><subject>Actins - physiology</subject><subject>Animals</subject><subject>Azepines - pharmacology</subject><subject>Capillary Permeability - drug effects</subject><subject>Capillary Permeability - physiology</subject><subject>Cytoskeleton - drug effects</subject><subject>Cytoskeleton - physiology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - physiology</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>histamine</subject><subject>Histamine - pharmacology</subject><subject>Male</subject><subject>Mesenteric Veins - drug effects</subject><subject>Mesenteric Veins - physiology</subject><subject>Microscopy, Fluorescence</subject><subject>myosin light chain kinase</subject><subject>Myosin-Light-Chain Kinase - antagonists & inhibitors</subject><subject>Naphthalenes - pharmacology</subject><subject>rat mesentery</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>thrombin</subject><subject>Thrombin - pharmacology</subject><subject>venular permeability</subject><subject>Venules - drug effects</subject><subject>Venules - physiology</subject><issn>1073-9688</issn><issn>1549-8719</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kD1PwzAQhi0EoqUwsqJMbCk-x4ntsYpKQS0fQkBHy0kvkNZJSpwI8u8JagUbk8-6517dPYScAx0DDeSVW4-LciwkpYyyAzKEkCtfClCHfU1F4KtIygE5cW5NKZWSqWMyAB6GQjI-JI9PlUWvyrzmHb1J2uSlF3dN5TZosalKr_8_4VtrTd9586blqupBmxvrPWJdoElymzfdD_aKZWvRnZKjzFiHZ_t3RF6up8_xjb94mN3Gk4WfBpGKfC4kV0kkQw4cJAIDRUPGEilNahSHTDGWCZZAIJBnEEnWH0tXEkRoslBEwYhc7nK3dfXRomt0kbsUrTUlVq3TApgA2gsYEX8HpnXlXI2Z3tZ5YepOA9U_CrVb66LUe4U9f7EPbpMCV3_03lkPwA74zC12_6fpu9s4DqK_JXLX4NfvjKk3OhKBCPXyfqZfb_ic8eVcL4NvIP6J8g</recordid><startdate>200310</startdate><enddate>200310</enddate><creator>VALESKI, J. EDWARD</creator><creator>BALDWIN, ANN L.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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>200310</creationdate><title>Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules</title><author>VALESKI, J. EDWARD ; BALDWIN, ANN L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3696-47849b68541418e12190522b88aca941f922f72b137e4f16820380d8175af5763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>actin cytoskeleton</topic><topic>Actins - physiology</topic><topic>Animals</topic><topic>Azepines - pharmacology</topic><topic>Capillary Permeability - drug effects</topic><topic>Capillary Permeability - physiology</topic><topic>Cytoskeleton - drug effects</topic><topic>Cytoskeleton - physiology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - physiology</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>histamine</topic><topic>Histamine - pharmacology</topic><topic>Male</topic><topic>Mesenteric Veins - drug effects</topic><topic>Mesenteric Veins - physiology</topic><topic>Microscopy, Fluorescence</topic><topic>myosin light chain kinase</topic><topic>Myosin-Light-Chain Kinase - antagonists & inhibitors</topic><topic>Naphthalenes - pharmacology</topic><topic>rat mesentery</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>thrombin</topic><topic>Thrombin - pharmacology</topic><topic>venular permeability</topic><topic>Venules - drug effects</topic><topic>Venules - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>VALESKI, J. EDWARD</creatorcontrib><creatorcontrib>BALDWIN, ANN L.</creatorcontrib><collection>Istex</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>Microcirculation (New York, N.Y. 1994)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>VALESKI, J. EDWARD</au><au>BALDWIN, ANN L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules</atitle><jtitle>Microcirculation (New York, N.Y. 1994)</jtitle><addtitle>Microcirculation</addtitle><date>2003-10</date><risdate>2003</risdate><volume>10</volume><issue>5</issue><spage>411</spage><epage>420</epage><pages>411-420</pages><issn>1073-9688</issn><eissn>1549-8719</eissn><abstract>ABSTRACT
Objective: This study was performed to determine the effect of myosin light chain kinase (MLCK) inhibition on histamine‐ and thrombin‐induced venular permeability in the rat mesentery, coincidental with actin cytoskeleton changes.
Methods: The mesenteric microvasculature of rats was perfused with a fluorescent tracer plus thrombin, histamine, or buffered saline, and the preparation was suffused with the MLCK inhibitor ML‐7. The microvasculature then was stained for actin.
Results: The average (±SE) number of leaks per micrometer of venule length of the thrombin plus 5 µM ML‐7 treatment (35.3 ± 5.9 × 10−4; n = 224) was significantly lower than that for the thrombin‐only treatment (61.7 ± 5.6 × 10−4; n = 385; p < 0.001). The histamine preparations required higher concentrations of ML‐7 to significantly reduce the number of leaks. A concentration of 100 µM reduced the average leak number from 20.8 ± 3.9 × 10 4 (n = 140) to 2.5 ± 0.8 × 10−4 (n = 383; p < 0.001), but 20 µM ML‐7 had no effect. Although leaky areas of both the thrombin‐ and histamine‐treated preparations showed disruptions of the peripheral actin rim coincident with fluorescein isothiocyanate‐bovine serum albumin leaks, qualitative and quantitative differences were identified.
Conclusions: The results suggest both similar and dissimilar mechanisms for thrombin and histamine regarding in situ endothelial gap formation.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>14557824</pmid><doi>10.1038/sj.mn.7800202</doi><tpages>10</tpages></addata></record> |
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| subjects | actin cytoskeleton Actins - physiology Animals Azepines - pharmacology Capillary Permeability - drug effects Capillary Permeability - physiology Cytoskeleton - drug effects Cytoskeleton - physiology Endothelium, Vascular - drug effects Endothelium, Vascular - physiology Enzyme Inhibitors - pharmacology histamine Histamine - pharmacology Male Mesenteric Veins - drug effects Mesenteric Veins - physiology Microscopy, Fluorescence myosin light chain kinase Myosin-Light-Chain Kinase - antagonists & inhibitors Naphthalenes - pharmacology rat mesentery Rats Rats, Sprague-Dawley thrombin Thrombin - pharmacology venular permeability Venules - drug effects Venules - physiology |
| title | Role of the Actin Cytoskeleton in Regulating Endothelial Permeability in Venules |
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