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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Veröffentlicht in:The Journal of clinical investigation 1993-05, Vol.91 (5), p.2012-2019
Hauptverfasser: SADAYOSHI ITO, SHUJI ARIMA, YI LIN REN, JUNCOS, L. A, CARRETERO, O. A
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container_end_page 2019
container_issue 5
container_start_page 2012
container_title The Journal of clinical investigation
container_volume 91
creator SADAYOSHI ITO
SHUJI ARIMA
YI LIN REN
JUNCOS, L. A
CARRETERO, O. A
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 &lt; 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. 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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 &lt; 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 &amp; 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. 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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 &lt; 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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