{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T12:31:44Z","timestamp":1753360304453},"reference-count":37,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p> Bradykinin\u00a02 receptor (B2R) deficiency predisposes to cardiac hypertrophy and hypertension. The pathways mediating these effects are not known. Two-month-old B2R knockout (KO) and wild-type (WT) mice were assigned to 4 treatment groups (n\u00a0= 12\u201314\/group): control (vehicle); nitro-l-arginine methyl ester (l-NAME) an NO synthase inhibitor; simvastatin (SIM), an NO synthase activator; and SIM+l-NAME. Serial echocardiography was performed and blood pressure (BP) at 6\u00a0weeks was recorded using a micromanometer. Myocardial eNOS and mitogen-activated protein kinase (MAPK, including ERK, p38, and JNK) protein expression were measured. Results showed that (i)\u00a0B2RKO mice had significantly lower ejection fraction than did WT mice (61%\u00a0\u00b1 1% vs. 73%\u00a0\u00b1 1%), lower myocardial eNOS and phospho-eNOS, normal systolic BP, and higher LV mass, phospho-p38, and JNK; (ii)\u00a0l-NAME increased systolic BP in KO mice (117\u00a0\u00b1 19\u00a0mm\u2009Hg) but not in WT mice and exacerbated LV hypertrophy and dysfunction; and (iii)\u00a0in KO mice, SIM decreased hypertrophy, p38, and JNK, improved function, increased capillary eNOS and phospho-eNOS, and prevented l-NAME-induced LV hypertrophy without lowering BP. We conclude that disruption of the B2R causes maladaptive cardiac hypertrophy with myocardial eNOS downregulation and MAPK upregulation. SIM reverses these abnormalities and prevents the development of primary cardiac hypertrophy as well as hypertrophy secondary to l-NAME-induced hypertension. <\/jats:p>","DOI":"10.1139\/y08-068","type":"journal-article","created":{"date-parts":[[2008,8,29]],"date-time":"2008-08-29T18:15:18Z","timestamp":1220033718000},"page":"633-642","source":"Crossref","is-referenced-by-count":10,"title":["Simvastatin reverses cardiac hypertrophy caused by disruption of the bradykinin\u00a02 receptorPresented in part at the American College of Cardiology meeting March 2003 in Orlando, USA, and the Society for Pediatric Research meeting May 2007 in Toronto, Canada."],"prefix":"10.1139","volume":"86","author":[{"given":"Juan C.","family":"Osorio","sequence":"first","affiliation":[{"name":"Columbia University, New York, NY, USA."},{"name":"Hospital for Sick Children, Toronto, Ontario, Canada."},{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Morgan Stanley Children\u2019s Hospital of New York Presbyterian, Columbia University, New York, NY, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faisal H.","family":"Cheema","sequence":"additional","affiliation":[{"name":"Columbia University, New York, NY, USA."},{"name":"Hospital for Sick Children, Toronto, Ontario, Canada."},{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Morgan Stanley Children\u2019s Hospital of New York Presbyterian, Columbia University, New York, NY, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy P.","family":"Martens","sequence":"additional","affiliation":[{"name":"Columbia University, New York, NY, USA."},{"name":"Hospital for Sick Children, Toronto, Ontario, Canada."},{"name":"Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA."},{"name":"Morgan Stanley Children\u2019s Hospital of New York Presbyterian, Columbia University, New York, NY, 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