{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T19:28:47Z","timestamp":1760297327290},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,30]],"date-time":"2009-01-30T00:00:00Z","timestamp":1233273600000},"content-version":"vor","delay-in-days":3286,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The effects on the responses to coronary artery occlusion of a combined ACE\/NEP inhibitor (Z13752A) were examined in anaesthetized dogs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>A 1\u2003h infusion of Z13752A (128\u2003\u03bcg\u2003kg<jats:sup>\u22121<\/jats:sup>\u2003min<jats:sup>\u22121<\/jats:sup> intravenously) decreased arterial blood pressure (by 11\u00b13%; <jats:italic>P<\/jats:italic>&lt;0.05) and increased coronary blood flow (by 12\u00b14%, <jats:italic>P<\/jats:italic>&lt;0.05). There were no other significant haemodynamic changes.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Z13752A inhibited both NEP and ACE enzymes both in dog plasma and in tissue (lung ACE; kidney NEP). Pressor responses to angiotensin I <jats:italic>in vivo<\/jats:italic> were inhibited and systemic vasodilator responses to bradykinin were potentiated.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When the left anterior descending coronary artery was occluded for 25\u2003min, Z13752A markedly reduced the severity of the resultant ventricular arrhythmias. No ventricular fibrillation (VF) occurred (compared to 7\/16 in the controls; <jats:italic>P<\/jats:italic>&lt;0.05), and ventricular tachycardia (VT) was reduced (VT in 2\/9 dogs treated with Z13752A cp. 16\/16 of controls; episodes of VT 0.2\u00b10.1 c.p. 10.7\u00b13.3; <jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Reperfusion of the ischaemic myocardium led to VF in all control dogs but occurred less frequently in dogs given Z13752A (survival from the combined ischaemia\u2010reperfusion insult 67% c.p. 0% in controls; <jats:italic>P<\/jats:italic>&lt;0.05).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Z13752A reduced two other indices of ischaemia severity; epicardial ST\u2010segment elevation and inhomogeneity of electrical activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These protective effects of Z13752A during ischaemia and reperfusion were abolished by the administration of icatibant (0.3\u2003mg\u2003kg<jats:sup>\u22121<\/jats:sup>, i.v.) a selective antagonist of bradykinin at B<jats:sub>2<\/jats:sub> receptors; the ischaemic changes in dogs given both icatibant and Z13752A were similar to those in the controls.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that this ACE\/NEP inhibitor is effective at reducing the consequences of coronary artery occlusion in this canine model and that this protection is primarily due to potentiation of released bradykinin.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>129<\/jats:bold>, 671\u2013680; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0703109\">10.1038\/sj.bjp.0703109<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0703109","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T20:46:01Z","timestamp":1106945161000},"page":"671-680","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The effects of Z13752A, a combined ACE\/NEP inhibitor, on responses to coronary artery occlusion; a primary protective role for bradykinin"],"prefix":"10.1111","volume":"129","author":[{"given":"Mohamed Ali","family":"Rastegar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Marchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabrielle","family":"Morazzoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes","family":"V\u00e9gh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julius Gy","family":"Papp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R","family":"Parratt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,1,30]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701619"},{"key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1097\/00005344-198411000-00009","article-title":"Effects of captopril on limiting infarct size in conscious dogs","volume":"6","author":"DANIELL H.B.","year":"1984","journal-title":"J. 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