{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:52:01Z","timestamp":1791161521860,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:00:00Z","timestamp":1791072000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>\n                      Kininase I, comprising carboxypeptidase N (CPN) and carboxypeptidase M, regulates kinin activity and is up\u2010regulated during injury, inflammation and immune activation. Under these conditions, kininase I converts bradykinin and kallidin into des\u2010Arg kinins, primary endogenous agonists of the bradykinin B\n                      <jats:sub>1<\/jats:sub>\n                      receptor (R). B\n                      <jats:sub>1<\/jats:sub>\n                      R signalling promotes vasoconstriction and inflammatory responses in the pathogenesis of hypertension. The roles of kininase I in regulating kinin\u2010dependent signalling and inter\u2010system interactions that contribute to blood pressure control and hypertensive organ injury remain poorly defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>CPN knockout (CPNKO) and wild\u2010type (WT) mice underwent chronic Ang II infusion to evaluate the role of CPN, and a separate cohort of WT mice were treated with the kininase I inhibitor Mergetpa alongside angiotensin (Ang) II to assess the effects of kininase I inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      Ang II in WT mice increased blood pressure and was accompanied by sympathetic overactivation, increased B\n                      <jats:sub>1<\/jats:sub>\n                      R expression, cardiac remodelling, immune cell infiltration and complement activation. CPNKO mice exhibited attenuated Ang II\u2010induced hypertension, reduced B\n                      <jats:sub>1<\/jats:sub>\n                      receptor expression, decreased cardiac fibrosis and blunted sympathetic activation. Pharmacologic inhibition of kininase I with Mergetpa reduced Ang II\u2010induced increases in blood pressure, limited B\n                      <jats:sub>1<\/jats:sub>\n                      R up\u2010regulation and suppressed complement activation and immune cell infiltration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These findings identify kininase I as a critical enzymatic regulator linking the renin angiotensin and kallikrein kinin systems and highlight a mechanism through which cardiovascular and immune signalling pathways interact to drive hypertension. These results position kininase I as a potential therapeutic target for the treatment of hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70692","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:07:27Z","timestamp":1791158847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Kininase I drives angiotensin II\u2010induced hypertension through activation of the bradykinin B\n                    <sub>1<\/sub>\n                    receptor"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-7663","authenticated-orcid":false,"given":"Acacia","family":"White","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6534-0909","authenticated-orcid":false,"given":"Drew","family":"Theobald","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4365-8222","authenticated-orcid":false,"given":"Alexandra","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3490-2283","authenticated-orcid":false,"given":"David A.","family":"Tulis","sequence":"additional","affiliation":[{"name":"Department of Physiology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8469-8105","authenticated-orcid":false,"given":"Johanna","family":"Hannan","sequence":"additional","affiliation":[{"name":"Department of Physiology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"},{"name":"Department of Urology, School of Medicine and Public Health University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-1589","authenticated-orcid":false,"given":"Srinivas","family":"Sriramula","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Brody School of Medicine at East Carolina University  Greenville North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,4]]},"reference":[{"issue":"6","key":"e_1_2_12_2_1","first-page":"798","article-title":"Conversion of MM creatine kinase isoforms in human plasma by carboxypeptidase N","volume":"110","author":"Abendschein D. 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