In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints
Background and purpose: Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor‐me...
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Veröffentlicht in: | British journal of pharmacology 2008-01, Vol.153 (2), p.358-366 |
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description | Background and purpose:
Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor‐mediated responses was also tested.
Experimental approach:
Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees.
Key results:
In normal animals, JWH015 and JWH133 caused a concentration‐dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid‐1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow.
Conclusion and implications:
In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated.
British Journal of Pharmacology (2008) 153, 358–366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007 |
doi_str_mv | 10.1038/sj.bjp.0707565 |
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fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2219539</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1416457031</sourcerecordid><originalsourceid>FETCH-LOGICAL-p3041-72f0387e42db4e830e26148ef8ad90a84689e6150a0d7c34b52f3c02e5aca60d3</originalsourceid><addsrcrecordid>eNpVkc1u1DAUhS1ERYfCliWy2GfwX2Jng0RHQCtVKgtYW45zwzhk7GA7qbrjEXjGPgmuOkBZ3cV37rk_B6FXlGwp4eptGrfdOG-JJLJu6idoQ4Vsqpor-hRtCCGyolSpU_Q8pZGQAmX9DJ1S2SompNigdOnx6taAYRjA5oTDgHfnDEewMOcQ737-SjAV4lbA1nhvOueD64vQ47wHvJpkl8nkJcJ9rw_xYCZsfI9NzPvosrM4moy_ewA8BudzeoFOBjMleHmsZ-jrxw9fdhfV1fWny937q2rmRNBKsqFcKEGwvhOgOAHWUKFgUKZviVGiUS00tCaG9NJy0dVs4JYwqI01Den5GXr34Dsv3QF6Cz5HM-k5uoOJtzoYp_8n3u31t7Bqxmhb87YYvDkaxPBjgZT1GJboy86aUckoV4QX0evHU_7a__lxEbAHwY2b4PYfJ_o-QZ1GXRLUxwT1-eeLRlH-GwrikZg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>217213803</pqid></control><display><type>article</type><title>In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>McDougall, J J ; Yu, V ; Thomson, J</creator><creatorcontrib>McDougall, J J ; Yu, V ; Thomson, J</creatorcontrib><description>Background and purpose:
Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor‐mediated responses was also tested.
Experimental approach:
Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees.
Key results:
In normal animals, JWH015 and JWH133 caused a concentration‐dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid‐1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow.
Conclusion and implications:
In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated.
British Journal of Pharmacology (2008) 153, 358–366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1038/sj.bjp.0707565</identifier><identifier>PMID: 17982474</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Administration, Topical ; Animals ; arthritis ; Arthritis, Experimental - physiopathology ; blood flow ; Blood Pressure - drug effects ; cannabinoids ; Cannabinoids - administration & dosage ; Cannabinoids - pharmacology ; cardiovascular system ; CB2 receptor ; Dose-Response Relationship, Drug ; Edema - drug therapy ; Edema - pathology ; endocannabinoids ; Image Processing, Computer-Assisted ; Joints - blood supply ; Joints - drug effects ; knee joint ; laser doppler imaging ; Male ; Rats ; Rats, Wistar ; Receptor, Cannabinoid, CB2 - drug effects ; Regional Blood Flow - drug effects ; Research Papers ; transient potential vanilloid receptor ; TRPV Cation Channels - genetics ; Vasodilator Agents - pharmacology</subject><ispartof>British journal of pharmacology, 2008-01, Vol.153 (2), p.358-366</ispartof><rights>2008 British Pharmacological Society</rights><rights>Copyright Nature Publishing Group Jan 2008</rights><rights>Copyright 2008, Nature Publishing Group 2008 Nature Publishing Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219539/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219539/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17982474$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McDougall, J J</creatorcontrib><creatorcontrib>Yu, V</creatorcontrib><creatorcontrib>Thomson, J</creatorcontrib><title>In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and purpose:
Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor‐mediated responses was also tested.
Experimental approach:
Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees.
Key results:
In normal animals, JWH015 and JWH133 caused a concentration‐dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid‐1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow.
Conclusion and implications:
In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated.
British Journal of Pharmacology (2008) 153, 358–366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007</description><subject>Administration, Topical</subject><subject>Animals</subject><subject>arthritis</subject><subject>Arthritis, Experimental - physiopathology</subject><subject>blood flow</subject><subject>Blood Pressure - drug effects</subject><subject>cannabinoids</subject><subject>Cannabinoids - administration & dosage</subject><subject>Cannabinoids - pharmacology</subject><subject>cardiovascular system</subject><subject>CB2 receptor</subject><subject>Dose-Response Relationship, Drug</subject><subject>Edema - drug therapy</subject><subject>Edema - pathology</subject><subject>endocannabinoids</subject><subject>Image Processing, Computer-Assisted</subject><subject>Joints - blood supply</subject><subject>Joints - drug effects</subject><subject>knee joint</subject><subject>laser doppler imaging</subject><subject>Male</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Cannabinoid, CB2 - drug effects</subject><subject>Regional Blood Flow - drug effects</subject><subject>Research Papers</subject><subject>transient potential vanilloid receptor</subject><subject>TRPV Cation Channels - genetics</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpVkc1u1DAUhS1ERYfCliWy2GfwX2Jng0RHQCtVKgtYW45zwzhk7GA7qbrjEXjGPgmuOkBZ3cV37rk_B6FXlGwp4eptGrfdOG-JJLJu6idoQ4Vsqpor-hRtCCGyolSpU_Q8pZGQAmX9DJ1S2SompNigdOnx6taAYRjA5oTDgHfnDEewMOcQ737-SjAV4lbA1nhvOueD64vQ47wHvJpkl8nkJcJ9rw_xYCZsfI9NzPvosrM4moy_ewA8BudzeoFOBjMleHmsZ-jrxw9fdhfV1fWny937q2rmRNBKsqFcKEGwvhOgOAHWUKFgUKZviVGiUS00tCaG9NJy0dVs4JYwqI01Den5GXr34Dsv3QF6Cz5HM-k5uoOJtzoYp_8n3u31t7Bqxmhb87YYvDkaxPBjgZT1GJboy86aUckoV4QX0evHU_7a__lxEbAHwY2b4PYfJ_o-QZ1GXRLUxwT1-eeLRlH-GwrikZg</recordid><startdate>200801</startdate><enddate>200801</enddate><creator>McDougall, J J</creator><creator>Yu, V</creator><creator>Thomson, J</creator><general>Blackwell Publishing Ltd</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>200801</creationdate><title>In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints</title><author>McDougall, J J ; Yu, V ; Thomson, J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p3041-72f0387e42db4e830e26148ef8ad90a84689e6150a0d7c34b52f3c02e5aca60d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Administration, Topical</topic><topic>Animals</topic><topic>arthritis</topic><topic>Arthritis, Experimental - physiopathology</topic><topic>blood flow</topic><topic>Blood Pressure - drug effects</topic><topic>cannabinoids</topic><topic>Cannabinoids - administration & dosage</topic><topic>Cannabinoids - pharmacology</topic><topic>cardiovascular system</topic><topic>CB2 receptor</topic><topic>Dose-Response Relationship, Drug</topic><topic>Edema - drug therapy</topic><topic>Edema - pathology</topic><topic>endocannabinoids</topic><topic>Image Processing, Computer-Assisted</topic><topic>Joints - blood supply</topic><topic>Joints - drug effects</topic><topic>knee joint</topic><topic>laser doppler imaging</topic><topic>Male</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Cannabinoid, CB2 - drug effects</topic><topic>Regional Blood Flow - drug effects</topic><topic>Research Papers</topic><topic>transient potential vanilloid receptor</topic><topic>TRPV Cation Channels - genetics</topic><topic>Vasodilator Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McDougall, J J</creatorcontrib><creatorcontrib>Yu, V</creatorcontrib><creatorcontrib>Thomson, J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</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>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</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>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McDougall, J J</au><au>Yu, V</au><au>Thomson, J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2008-01</date><risdate>2008</risdate><volume>153</volume><issue>2</issue><spage>358</spage><epage>366</epage><pages>358-366</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and purpose:
Cannabinoids (CBs) are known to be vasoactive and to regulate tissue inflammation. The present study examined the in vivo vasomotor effects of the CB2 receptor agonists JWH015 and JWH133 in rat knee joints. The effect of acute and chronic joint inflammation on CB2 receptor‐mediated responses was also tested.
Experimental approach:
Blood flow was assessed in rat knee joints by laser Doppler imaging both before and following topical administration of CB2 receptor agonists. Vasoactivity was measured in normal, acute kaolin/carrageenan inflamed and Freund's complete adjuvant chronically inflamed knees.
Key results:
In normal animals, JWH015 and JWH133 caused a concentration‐dependent increase in synovial blood flow which in the case of JWH133 was blocked by the selective CB2 receptor antagonist AM630 as well as the transient receptor potential vanilloid‐1 (TRPV1) antagonist SB366791. The vasodilator effect of JWH133 was significantly attenuated in both acute and chronically inflamed knees. Given alone, AM630 had no effect on joint blood flow.
Conclusion and implications:
In normal joints, the cannabinomimetic JWH133 causes hyperaemia via a CB2 and TRPV1 receptor mechanism. During acute and chronic inflammation, however, this vasodilatatory response is significantly attenuated.
British Journal of Pharmacology (2008) 153, 358–366; doi:10.1038/sj.bjp.0707565; published online 5 November 2007</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>17982474</pmid><doi>10.1038/sj.bjp.0707565</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Administration, Topical Animals arthritis Arthritis, Experimental - physiopathology blood flow Blood Pressure - drug effects cannabinoids Cannabinoids - administration & dosage Cannabinoids - pharmacology cardiovascular system CB2 receptor Dose-Response Relationship, Drug Edema - drug therapy Edema - pathology endocannabinoids Image Processing, Computer-Assisted Joints - blood supply Joints - drug effects knee joint laser doppler imaging Male Rats Rats, Wistar Receptor, Cannabinoid, CB2 - drug effects Regional Blood Flow - drug effects Research Papers transient potential vanilloid receptor TRPV Cation Channels - genetics Vasodilator Agents - pharmacology |
title | In vivo effects of CB2 receptor‐selective cannabinoids on the vasculature of normal and arthritic rat knee joints |
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