A Local Kallikrein-Kinin System Is Present in Rat Hearts

It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an...

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Veröffentlicht in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 1994-06, Vol.23 (6, Part 2), p.919-923
Hauptverfasser: Nolly, Héctor, Carbini, Luis A, Scicli, Gloria, Carretero, Oscar A, Scicli, A Guillermo
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container_issue 6, Part 2
container_start_page 919
container_title Hypertension (Dallas, Tex. 1979)
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creator Nolly, Héctor
Carbini, Luis A
Scicli, Gloria
Carretero, Oscar A
Scicli, A Guillermo
description It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsinactivatable) kallikrein into the medium (46±5 and 380±18 pg bradykinin/mg, respectively, after 1 hour and 78±6 and 654±14 pg bradykinin/mg after 2 hours, n=7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9±2.9 to 2.9±1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423±25 pg bradykinin/mg in nonincubated slices and 370±42 pg bradykinin/mg after 2 hours, P=NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78±6 to 22±4 pg bradykinin/mg and total kallikrein from 654±14 to 113±9 pg bradykinin/mg (P
doi_str_mv 10.1161/01.hyp.23.6.919
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However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsinactivatable) kallikrein into the medium (46±5 and 380±18 pg bradykinin/mg, respectively, after 1 hour and 78±6 and 654±14 pg bradykinin/mg after 2 hours, n=7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9±2.9 to 2.9±1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423±25 pg bradykinin/mg in nonincubated slices and 370±42 pg bradykinin/mg after 2 hours, P=NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78±6 to 22±4 pg bradykinin/mg and total kallikrein from 654±14 to 113±9 pg bradykinin/mg (P&lt;.001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium. Kallikrein mRNA was present in both cell types. Heart slices also released kininogen (1375±78 pg bradykinin/mg). Release was inhibited by puromycin (P&lt;.001). These data demonstrate that the heart contains an independent kallikrein-kinin system. 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Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78±6 to 22±4 pg bradykinin/mg and total kallikrein from 654±14 to 113±9 pg bradykinin/mg (P&lt;.001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium. Kallikrein mRNA was present in both cell types. Heart slices also released kininogen (1375±78 pg bradykinin/mg). Release was inhibited by puromycin (P&lt;.001). These data demonstrate that the heart contains an independent kallikrein-kinin system. 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Psychology</subject><subject>Heart</subject><subject>Kallikreins - genetics</subject><subject>Kallikreins - metabolism</subject><subject>Kinins - metabolism</subject><subject>Male</subject><subject>Myocardium - cytology</subject><subject>Myocardium - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Protease Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - metabolism</subject><subject>Transcription, Genetic</subject><subject>Vertebrates: cardiovascular system</subject><issn>0194-911X</issn><issn>1524-4563</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpd0U1r3DAQBmBRWtJt2nNPBVNKbnY00kiWjiG02ZCFhn5AexKyPGadeO2tZBP231dllxyqi2Dm0TC8Yuw98ApAwyWHanvYV0JWurJgX7AVKIElKi1fshUHi6UF-PWavUnpgXNAxPqMnRnBtRZmxcxVsZmCH4o7Pwz9Y6R-LO_6sR-L74c00664TcV9pETjXOTiNz8Xa_JxTm_Zq84Pid6d7nP288vnH9frcvP15vb6alMGhSDL0HVto2pbE0rPsWtbD0Eq1REJoSy2hBS4kcEH0TWmMYa40cCDIdso1cpzdnGcu4_Tn4XS7HZ9CjQMfqRpSa7WSmiwdYYf_4MP0xLHvJsTPBuNAjO6PKIQp5QidW4f-52PBwfc_QvUcXDr3_dOSKddDjS_-HAauzQ7ap_9KcHc_3Tq-5Rz7KIfQ5-eGQJyYURmeGRP0zBTTI_D8kTRbckP89bxfFBoU4K1yHX-pzJXhJR_AbuNi7g</recordid><startdate>199406</startdate><enddate>199406</enddate><creator>Nolly, Héctor</creator><creator>Carbini, Luis A</creator><creator>Scicli, Gloria</creator><creator>Carretero, Oscar A</creator><creator>Scicli, A Guillermo</creator><general>American Heart Association, Inc</general><general>Lippincott</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>K9.</scope><scope>7X8</scope></search><sort><creationdate>199406</creationdate><title>A Local Kallikrein-Kinin System Is Present in Rat Hearts</title><author>Nolly, Héctor ; Carbini, Luis A ; Scicli, Gloria ; Carretero, Oscar A ; Scicli, A Guillermo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5413-cffdb5797e43a04fdda1c355fee22594de4ec083cac2fb8b88e08610c8e9b55d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Chromatography, Affinity</topic><topic>Electrophoresis, Polyacrylamide Gel</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Heart</topic><topic>Kallikreins - genetics</topic><topic>Kallikreins - metabolism</topic><topic>Kinins - metabolism</topic><topic>Male</topic><topic>Myocardium - cytology</topic><topic>Myocardium - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Protease Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - metabolism</topic><topic>Transcription, Genetic</topic><topic>Vertebrates: cardiovascular system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nolly, Héctor</creatorcontrib><creatorcontrib>Carbini, Luis A</creatorcontrib><creatorcontrib>Scicli, Gloria</creatorcontrib><creatorcontrib>Carretero, Oscar A</creatorcontrib><creatorcontrib>Scicli, A Guillermo</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>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nolly, Héctor</au><au>Carbini, Luis A</au><au>Scicli, Gloria</au><au>Carretero, Oscar A</au><au>Scicli, A Guillermo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Local Kallikrein-Kinin System Is Present in Rat Hearts</atitle><jtitle>Hypertension (Dallas, Tex. 1979)</jtitle><addtitle>Hypertension</addtitle><date>1994-06</date><risdate>1994</risdate><volume>23</volume><issue>6, Part 2</issue><spage>919</spage><epage>923</epage><pages>919-923</pages><issn>0194-911X</issn><eissn>1524-4563</eissn><coden>HPRTDN</coden><abstract>It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsinactivatable) kallikrein into the medium (46±5 and 380±18 pg bradykinin/mg, respectively, after 1 hour and 78±6 and 654±14 pg bradykinin/mg after 2 hours, n=7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9±2.9 to 2.9±1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423±25 pg bradykinin/mg in nonincubated slices and 370±42 pg bradykinin/mg after 2 hours, P=NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78±6 to 22±4 pg bradykinin/mg and total kallikrein from 654±14 to 113±9 pg bradykinin/mg (P&lt;.001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium. Kallikrein mRNA was present in both cell types. Heart slices also released kininogen (1375±78 pg bradykinin/mg). Release was inhibited by puromycin (P&lt;.001). These data demonstrate that the heart contains an independent kallikrein-kinin system. Locally generated kinins may help regulate cardiac function.</abstract><cop>Philadelphia, PA</cop><cop>Hagerstown, MD</cop><pub>American Heart Association, Inc</pub><pmid>8206628</pmid><doi>10.1161/01.hyp.23.6.919</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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source MEDLINE; American Heart Association Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Journals@Ovid Ovid Autoload
subjects Animals
Biological and medical sciences
Chromatography, Affinity
Electrophoresis, Polyacrylamide Gel
Fundamental and applied biological sciences. Psychology
Heart
Kallikreins - genetics
Kallikreins - metabolism
Kinins - metabolism
Male
Myocardium - cytology
Myocardium - metabolism
Polymerase Chain Reaction
Protease Inhibitors - pharmacology
Rats
Rats, Wistar
RNA, Messenger - metabolism
Transcription, Genetic
Vertebrates: cardiovascular system
title A Local Kallikrein-Kinin System Is Present in Rat Hearts
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