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 |
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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<.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<.001). These data demonstrate that the heart contains an independent kallikrein-kinin system. Locally generated kinins may help regulate cardiac function.</description><identifier>ISSN: 0194-911X</identifier><identifier>EISSN: 1524-4563</identifier><identifier>DOI: 10.1161/01.hyp.23.6.919</identifier><identifier>PMID: 8206628</identifier><identifier>CODEN: HPRTDN</identifier><language>eng</language><publisher>Philadelphia, PA: American Heart Association, Inc</publisher><subject>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</subject><ispartof>Hypertension (Dallas, Tex. 1979), 1994-06, Vol.23 (6, Part 2), p.919-923</ispartof><rights>1994 American Heart Association, Inc.</rights><rights>1994 INIST-CNRS</rights><rights>Copyright American Heart Association, Inc. Jun 1994</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5413-cffdb5797e43a04fdda1c355fee22594de4ec083cac2fb8b88e08610c8e9b55d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3687,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4140282$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8206628$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nolly, Héctor</creatorcontrib><creatorcontrib>Carbini, Luis A</creatorcontrib><creatorcontrib>Scicli, Gloria</creatorcontrib><creatorcontrib>Carretero, Oscar A</creatorcontrib><creatorcontrib>Scicli, A Guillermo</creatorcontrib><title>A Local Kallikrein-Kinin System Is Present in Rat Hearts</title><title>Hypertension (Dallas, Tex. 1979)</title><addtitle>Hypertension</addtitle><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<.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<.001). These data demonstrate that the heart contains an independent kallikrein-kinin system. Locally generated kinins may help regulate cardiac function.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Chromatography, Affinity</subject><subject>Electrophoresis, Polyacrylamide Gel</subject><subject>Fundamental and applied biological sciences. 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 & 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<.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<.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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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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