The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant
N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed usin...
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| Veröffentlicht in: | European journal of pharmacology 2017-01, Vol.794, p.209-215 |
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| description | N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3mg/kg). In resistant vessels, NAGLY (1–30µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300µM), a cGMP synthase inhibitor, ODQ (10µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3µM) and O-1918 (10µM) and the inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943 (10µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1 receptor antagonist), AM 630 (cannabinoid CB2 receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release. |
| doi_str_mv | 10.1016/j.ejphar.2016.11.040 |
| format | Article |
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This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3mg/kg). In resistant vessels, NAGLY (1–30µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300µM), a cGMP synthase inhibitor, ODQ (10µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3µM) and O-1918 (10µM) and the inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943 (10µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1 receptor antagonist), AM 630 (cannabinoid CB2 receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2016.11.040</identifier><identifier>PMID: 27890711</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Anilides - pharmacology ; Animals ; Anisoles - pharmacology ; Arachidonic Acids - pharmacology ; Blood Pressure - drug effects ; Capsaicin - analogs & derivatives ; Capsaicin - pharmacology ; Carbachol - pharmacology ; Cyclic GMP - metabolism ; Cyclohexanes - pharmacology ; Endothelium, Vascular - drug effects ; Endothelium, Vascular - metabolism ; Endothelium, Vascular - pathology ; Glycine - analogs & derivatives ; Glycine - pharmacology ; Hypertension - metabolism ; Hypertension - physiopathology ; Hypotensive ; Kidney - blood supply ; Kidney - drug effects ; Male ; N-arachidonoyl glycine ; Na+/Ca2+ exchanger ; NG-Nitroarginine Methyl Ester - pharmacology ; Nitric oxide ; Nitric Oxide - metabolism ; Oxadiazoles - pharmacology ; Phenylephrine - pharmacology ; Piperidines - pharmacology ; Potassium Channels, Calcium-Activated - antagonists & inhibitors ; Pyrazoles - pharmacology ; Quinoxalines - pharmacology ; Rats ; Rats, Wistar ; Regional Blood Flow - drug effects ; Thiourea - analogs & derivatives ; Thiourea - pharmacology ; Vasodilation - drug effects ; Vasorelaxation</subject><ispartof>European journal of pharmacology, 2017-01, Vol.794, p.209-215</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-628f6a41650d9895cc1e89246bbfbe4524c2d428e2f108c43418fbda11f7ffd43</citedby><cites>FETCH-LOGICAL-c362t-628f6a41650d9895cc1e89246bbfbe4524c2d428e2f108c43418fbda11f7ffd43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0014299916307439$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27890711$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Al Suleimani, Yousuf M.</creatorcontrib><creatorcontrib>Al Mahruqi, Ahmed S.</creatorcontrib><title>The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3mg/kg). In resistant vessels, NAGLY (1–30µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300µM), a cGMP synthase inhibitor, ODQ (10µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3µM) and O-1918 (10µM) and the inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943 (10µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1 receptor antagonist), AM 630 (cannabinoid CB2 receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release.</description><subject>Anilides - pharmacology</subject><subject>Animals</subject><subject>Anisoles - pharmacology</subject><subject>Arachidonic Acids - pharmacology</subject><subject>Blood Pressure - drug effects</subject><subject>Capsaicin - analogs & derivatives</subject><subject>Capsaicin - pharmacology</subject><subject>Carbachol - pharmacology</subject><subject>Cyclic GMP - metabolism</subject><subject>Cyclohexanes - pharmacology</subject><subject>Endothelium, Vascular - drug effects</subject><subject>Endothelium, Vascular - metabolism</subject><subject>Endothelium, Vascular - pathology</subject><subject>Glycine - analogs & derivatives</subject><subject>Glycine - pharmacology</subject><subject>Hypertension - metabolism</subject><subject>Hypertension - physiopathology</subject><subject>Hypotensive</subject><subject>Kidney - blood supply</subject><subject>Kidney - drug effects</subject><subject>Male</subject><subject>N-arachidonoyl glycine</subject><subject>Na+/Ca2+ exchanger</subject><subject>NG-Nitroarginine Methyl Ester - pharmacology</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Oxadiazoles - pharmacology</subject><subject>Phenylephrine - pharmacology</subject><subject>Piperidines - pharmacology</subject><subject>Potassium Channels, Calcium-Activated - antagonists & inhibitors</subject><subject>Pyrazoles - pharmacology</subject><subject>Quinoxalines - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Regional Blood Flow - drug effects</subject><subject>Thiourea - analogs & derivatives</subject><subject>Thiourea - pharmacology</subject><subject>Vasodilation - drug effects</subject><subject>Vasorelaxation</subject><issn>0014-2999</issn><issn>1879-0712</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFu1DAQhi0EotvCGyDkI5ekHsdJ7AsSqkpbqQUO5Ww59mTXq6wd7Oyq-_a42sKxp9FI38yv_yPkE7AaGHSX2xq388akmpetBqiZYG_ICmSvKtYDf0tWjIGouFLqjJznvGWMtYq378kZ76UqDKzI-nGDFIOLawxxn-nkZ-_oj8okYzfexRCPE11PR-sDUp_p5jjHBUP2B6QmOBr8kryl8ck7rOzNw6_K4Vz-YVjoweSYcDJPJiwfyLvRTBk_vswL8vv79ePVbXX_8-bu6tt9ZZuOL1XH5dgZAV3LnJKqtRZQKi66YRgHFC0XljvBJfIRmLSiESDHwRmAsR9HJ5oL8uX0d07xzx7zonc-W5wmE7D00yCFaNpG9W1BxQm1KeaccNRz8juTjhqYflast_qkWD8r1gC6KC5nn18S9sMO3f-jf04L8PUEYOl58Jh0th6DRecT2kW76F9P-AtM2JA3</recordid><startdate>20170105</startdate><enddate>20170105</enddate><creator>Al Suleimani, Yousuf M.</creator><creator>Al Mahruqi, Ahmed S.</creator><general>Elsevier B.V</general><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>20170105</creationdate><title>The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant</title><author>Al Suleimani, Yousuf M. ; Al Mahruqi, Ahmed S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-628f6a41650d9895cc1e89246bbfbe4524c2d428e2f108c43418fbda11f7ffd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Anilides - pharmacology</topic><topic>Animals</topic><topic>Anisoles - pharmacology</topic><topic>Arachidonic Acids - pharmacology</topic><topic>Blood Pressure - drug effects</topic><topic>Capsaicin - analogs & derivatives</topic><topic>Capsaicin - pharmacology</topic><topic>Carbachol - pharmacology</topic><topic>Cyclic GMP - metabolism</topic><topic>Cyclohexanes - pharmacology</topic><topic>Endothelium, Vascular - drug effects</topic><topic>Endothelium, Vascular - metabolism</topic><topic>Endothelium, Vascular - pathology</topic><topic>Glycine - analogs & derivatives</topic><topic>Glycine - pharmacology</topic><topic>Hypertension - metabolism</topic><topic>Hypertension - physiopathology</topic><topic>Hypotensive</topic><topic>Kidney - blood supply</topic><topic>Kidney - drug effects</topic><topic>Male</topic><topic>N-arachidonoyl glycine</topic><topic>Na+/Ca2+ exchanger</topic><topic>NG-Nitroarginine Methyl Ester - pharmacology</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Oxadiazoles - pharmacology</topic><topic>Phenylephrine - pharmacology</topic><topic>Piperidines - pharmacology</topic><topic>Potassium Channels, Calcium-Activated - antagonists & inhibitors</topic><topic>Pyrazoles - pharmacology</topic><topic>Quinoxalines - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Regional Blood Flow - drug effects</topic><topic>Thiourea - analogs & derivatives</topic><topic>Thiourea - pharmacology</topic><topic>Vasodilation - drug effects</topic><topic>Vasorelaxation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Al Suleimani, Yousuf M.</creatorcontrib><creatorcontrib>Al Mahruqi, Ahmed S.</creatorcontrib><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>Al Suleimani, Yousuf M.</au><au>Al Mahruqi, Ahmed S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>2017-01-05</date><risdate>2017</risdate><volume>794</volume><spage>209</spage><epage>215</epage><pages>209-215</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><abstract>N-arachidonoyl glycine (NAGLY), is the endogenous lipid that activates the G protein-couple receptor 18 (GPR18) with vasodilatory activity in resistance arteries. This study investigates its hemodynamic effects and mechanisms of vasorelaxation. Hemodynamic effects of NAGLY in rats were assessed using a Biopac system and its vascular responses were assessed using a wire myograph. NAGLY (1mg/kg) decreased blood pressure by 69.4±5.5% and reduced renal blood flow by 88±12% and the effects were not sensitive to inhibition by O-1918 (3mg/kg). In resistant vessels, NAGLY (1–30µM) induced concentration- and endothelium-dependent vasorelaxation and the effect was inhibited by the nitric oxide synthase inhibitor, L-NAME (300µM), a cGMP synthase inhibitor, ODQ (10µM), the antagonists of “endothelial anandamide” receptor, rimonabant (3µM) and O-1918 (10µM) and the inhibitor of Na+/Ca2+ exchanger (NCX), KB-R7943 (10µM). On the other hand, NAGLY-induced vasorelaxation was not affected by CID 16020046 (GPR55 antagonist), AM 251 (cannabinoid CB1 receptor antagonist), AM 630 (cannabinoid CB2 receptor antagonist), capsazepine (TRPV1 antagonist), indomethacin (cyclooxygenase inhibitor), TRAM34 (IKCa channel blocker), iberiotoxin (BKCa channel blocker) and GW9662 (PPARɤ antagonist). At low concentrations of carbachol, NAGLY potentiated carbachol-induced vasorelaxation. NAGLY is an endothelium-dependent vasodilator and hypotensive lipid. The vasorelaxation is predominantly via activation of nitric oxide-cGMP pathway and NCX and probably mediated by the "endothelial anandamide” receptor, while the hypotensive effect of NAGLY appears not to involve the anandamide receptor. NAGLY also potentiates carbachol-induced vasorelaxation, the mechanism of which might involve stimulation of NO release.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27890711</pmid><doi>10.1016/j.ejphar.2016.11.040</doi><tpages>7</tpages></addata></record> |
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| subjects | Anilides - pharmacology Animals Anisoles - pharmacology Arachidonic Acids - pharmacology Blood Pressure - drug effects Capsaicin - analogs & derivatives Capsaicin - pharmacology Carbachol - pharmacology Cyclic GMP - metabolism Cyclohexanes - pharmacology Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Endothelium, Vascular - pathology Glycine - analogs & derivatives Glycine - pharmacology Hypertension - metabolism Hypertension - physiopathology Hypotensive Kidney - blood supply Kidney - drug effects Male N-arachidonoyl glycine Na+/Ca2+ exchanger NG-Nitroarginine Methyl Ester - pharmacology Nitric oxide Nitric Oxide - metabolism Oxadiazoles - pharmacology Phenylephrine - pharmacology Piperidines - pharmacology Potassium Channels, Calcium-Activated - antagonists & inhibitors Pyrazoles - pharmacology Quinoxalines - pharmacology Rats Rats, Wistar Regional Blood Flow - drug effects Thiourea - analogs & derivatives Thiourea - pharmacology Vasodilation - drug effects Vasorelaxation |
| title | The endogenous lipid N-arachidonoyl glycine is hypotensive and nitric oxide-cGMP-dependent vasorelaxant |
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