Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole
It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit...
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description | It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II. |
doi_str_mv | 10.1172/JCI116423 |
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A ; CARRETERO, O. A</creator><creatorcontrib>SADAYOSHI ITO ; SHUJI ARIMA ; YI LIN REN ; JUNCOS, L. A ; CARRETERO, O. A</creatorcontrib><description>It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI116423</identifier><identifier>PMID: 8486771</identifier><identifier>CODEN: JCINAO</identifier><language>eng</language><publisher>Ann Arbor, MI: American Society for Clinical Investigation</publisher><subject>Angiotensin II - pharmacology ; Animals ; Arginine - analogs & derivatives ; Arginine - pharmacology ; Arterioles - drug effects ; Arterioles - physiology ; Biological and medical sciences ; Dose-Response Relationship, Drug ; Hematology ; In Vitro Techniques ; Investigative techniques, diagnostic techniques (general aspects) ; Kidney - blood supply ; Kinetics ; Male ; Medical sciences ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; NG-Nitroarginine Methyl Ester ; Nitric Oxide - metabolism ; Nitric Oxide - physiology ; Nitroarginine ; Norepinephrine - pharmacology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Perfusion ; Rabbits ; Vasoconstriction - drug effects</subject><ispartof>The Journal of clinical investigation, 1993-05, Vol.91 (5), p.2012-2019</ispartof><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-9fac01c477b33ed8f1bcc216f43f7159d46a0b45de28d0ce57295af95f025d253</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC288199/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC288199/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,724,777,781,882,27906,27907,53773,53775</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4743933$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8486771$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SADAYOSHI ITO</creatorcontrib><creatorcontrib>SHUJI ARIMA</creatorcontrib><creatorcontrib>YI LIN REN</creatorcontrib><creatorcontrib>JUNCOS, L. A</creatorcontrib><creatorcontrib>CARRETERO, O. A</creatorcontrib><title>Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II.</description><subject>Angiotensin II - pharmacology</subject><subject>Animals</subject><subject>Arginine - analogs & derivatives</subject><subject>Arginine - pharmacology</subject><subject>Arterioles - drug effects</subject><subject>Arterioles - physiology</subject><subject>Biological and medical sciences</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hematology</subject><subject>In Vitro Techniques</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Kidney - blood supply</subject><subject>Kinetics</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>NG-Nitroarginine Methyl Ester</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide - physiology</subject><subject>Nitroarginine</subject><subject>Norepinephrine - pharmacology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Perfusion</subject><subject>Rabbits</subject><subject>Vasoconstriction - drug effects</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1uEzEUhS1EVUJhwQMgeYEqsRjq39izYIGiAkGVuoH1yGNfp0YzdrA9VXkU3raOGiJYWfb57rlHPgi9oeQDpYpdfdtsKV0Lxp-hFZVSd5px_RytCGG06xXXL9DLUn4SQoWQ4hyda6HXStEV-nMdXap3MIVl7hzkcA8OZ5jMQ4g77I2tKV_FUHOwOD0EB3hObplMhYJN3IVUIZYQ8XaLGxtSxO3S_HAo6UA5PAeb0x6yX8rB2oxjqNh4DxlixeNScUwVw98Hk2tLkSZ4hc68mQq8Pp4X6Mfn6--br93N7Zft5tNNZ3mva9e3jIRaodTIOTjt6Wgto2svuFdU9k6sDRmFdMC0IxakYr00vpeeMOmY5Bfo45PvfhlncLaFyGYa9jnMJv8ekgnD_0oMd8Mu3Q9Ma9r3bf7yOJ_TrwVKHeZQLEyTiZCWMqi2kTCmG_j-CWz_UUoGf9pByXCocTjV2Ni3_4Y6kcfemv7uqJtizeSziTaUEyaU4D3n_BFCJaoY</recordid><startdate>19930501</startdate><enddate>19930501</enddate><creator>SADAYOSHI ITO</creator><creator>SHUJI ARIMA</creator><creator>YI LIN REN</creator><creator>JUNCOS, L. A</creator><creator>CARRETERO, O. A</creator><general>American Society for Clinical Investigation</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><scope>5PM</scope></search><sort><creationdate>19930501</creationdate><title>Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole</title><author>SADAYOSHI ITO ; SHUJI ARIMA ; YI LIN REN ; JUNCOS, L. A ; CARRETERO, O. A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c398t-9fac01c477b33ed8f1bcc216f43f7159d46a0b45de28d0ce57295af95f025d253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Angiotensin II - pharmacology</topic><topic>Animals</topic><topic>Arginine - analogs & derivatives</topic><topic>Arginine - pharmacology</topic><topic>Arterioles - drug effects</topic><topic>Arterioles - physiology</topic><topic>Biological and medical sciences</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hematology</topic><topic>In Vitro Techniques</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Kidney - blood supply</topic><topic>Kinetics</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>NG-Nitroarginine Methyl Ester</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide - physiology</topic><topic>Nitroarginine</topic><topic>Norepinephrine - pharmacology</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Perfusion</topic><topic>Rabbits</topic><topic>Vasoconstriction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SADAYOSHI ITO</creatorcontrib><creatorcontrib>SHUJI ARIMA</creatorcontrib><creatorcontrib>YI LIN REN</creatorcontrib><creatorcontrib>JUNCOS, L. A</creatorcontrib><creatorcontrib>CARRETERO, O. A</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SADAYOSHI ITO</au><au>SHUJI ARIMA</au><au>YI LIN REN</au><au>JUNCOS, L. A</au><au>CARRETERO, O. A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>1993-05-01</date><risdate>1993</risdate><volume>91</volume><issue>5</issue><spage>2012</spage><epage>2019</epage><pages>2012-2019</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><coden>JCINAO</coden><abstract>It has been reported that sensitivity to angiotensin II (Ang II) is higher in efferent (Ef) than afferent (Af) arterioles (Arts). We tested the hypothesis that this is due to arteriolar differences in the interaction between Ang II and endothelium-derived relaxing factor/nitric oxide (EDNO). Rabbit Af-Arts with glomerulus intact were microperfused in vitro at a constant pressure. Ef-Arts were perfused from the distal end of either the Af-Art (orthograde perfusion) or the Ef-Art (retrograde perfusion) to eliminate influences of the Af-Art or glomerulus, respectively. Ang II did not alter Af-Art luminal diameter until the concentration reached 10(-9) M, which decreased the diameter by 11 +/- 2.6% (n = 11; P < 0.002). In contrast, Ef-Arts became significantly constricted at concentrations as low as 10(-11) M with either perfusion. Surprisingly, the decrease in Ef-Art diameter at 10(-10), 10(-9), and 10(-8) M was significantly greater with retrograde perfusion (44 +/- 6.9%, 70 +/- 5.6%, and 74 +/- 4.1%, respectively; n = 5) than with orthograde perfusion (16 +/- 4.2%, 25 +/- 2.9%, and 35 +/- 3.5%; n = 9). ENDO synthesis inhibition with 10(-4) M nitro-L-arginine methyl ester (L-NAME) decreased the diameter to a greater extent in Af-Arts (22 +/- 3.0%; n = 11) compared to Ef-Arts with either orthograde (9.5 +/- 2.3%; n = 8) or retrograde perfusion (1.2 +/- 2.1%; n = 6). With L-NAME pretreatment, Af-Art constriction induced by 10(-10) M (14 +/- 4.0%, n = 9) and 10(-9) M Ang II (38 +/- 3.9%) was significantly greater compared to nontreated Af-Arts. In contrast, L-NAME pretreatment had no effect on Ang II-induced constriction in Ef-Arts with either perfusion. In conclusion, this study demonstrates higher sensitivity of Ef-Arts to Ang II, particularly with retrograde perfusion. Our results suggest that EDNO significantly modulates the vasoconstrictor action of Ang II in Af-Arts II but not Ef-Arts, contributing to the differential sensitivity to Ang II.</abstract><cop>Ann Arbor, MI</cop><pub>American Society for Clinical Investigation</pub><pmid>8486771</pmid><doi>10.1172/JCI116423</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Angiotensin II - pharmacology Animals Arginine - analogs & derivatives Arginine - pharmacology Arterioles - drug effects Arterioles - physiology Biological and medical sciences Dose-Response Relationship, Drug Hematology In Vitro Techniques Investigative techniques, diagnostic techniques (general aspects) Kidney - blood supply Kinetics Male Medical sciences Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology NG-Nitroarginine Methyl Ester Nitric Oxide - metabolism Nitric Oxide - physiology Nitroarginine Norepinephrine - pharmacology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Perfusion Rabbits Vasoconstriction - drug effects |
title | Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole |
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