{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T05:00:32Z","timestamp":1754110832288},"reference-count":39,"publisher":"Canadian Science Publishing","issue":"9","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9]]},"abstract":"<jats:p> Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1\u00b1 0.18\u00a0mm from 4.6\u00a0\u00b1 0.13\u00a0mm (p\u00a0&lt; 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1\u00a0\u00b1 0.1\u00a0mm and 4.8\u00a0\u00b1 0.2\u00a0mm, respectively (p\u00a0&lt; 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131%\u00a0\u00b1 3% of the control value, which was associated with significant increment in ERK1\/2 to 143%\u00a0\u00b1 5% of the control value (p\u00a0&lt; 0.05). Ordonafil and sildenafil decreased cell surface area to 95%\u00a0\u00b1 3% and 90%\u00a0\u00b1 1% of the control value, respectively. Both drugs decreased ERK1\/2 to 88%\u00a0\u00b1 4% of the control value. Calcineurin activity was significantly decreased after 1\u00a0h of treatment with 0.1\u00a0mg\u00b7L<jats:sup>\u20131<\/jats:sup> ordonafil (1.15\u00a0\u00b1 0.05, p\u00a0&lt; 0.05). For sildenafil (0.1\u00a0mg\u00b7L<jats:sup>\u20131<\/jats:sup>), calcineurin activity significantly decreased only after 24\u00a0h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1\u00a0mg\u00b7L<jats:sup>\u20131<\/jats:sup>). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes. <\/jats:p>","DOI":"10.1139\/y2012-098","type":"journal-article","created":{"date-parts":[[2012,8,24]],"date-time":"2012-08-24T13:29:05Z","timestamp":1345814945000},"page":"1247-1255","source":"Crossref","is-referenced-by-count":6,"title":["The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse <scp>L<\/scp>-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38"],"prefix":"10.1139","volume":"90","author":[{"given":"Asad","family":"Zeidan","sequence":"first","affiliation":[{"name":"Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiad","family":"Siam","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz","family":"Al Kaabba","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, King Fahad Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11525, Kingdom of Saudi Arabia."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mukhallad","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Said","family":"Khatib","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1038\/27094"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.23.6341"},{"key":"refg4\/ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.06.183"},{"key":"refg5\/ref5","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200868030-00009"},{"key":"refg6\/ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(99)00929-2"},{"key":"refg7\/ref7","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijir.3900908"},{"key":"refg8\/ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.04.039"},{"key":"refg10\/ref10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162100799"},{"key":"refg11\/ref11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.78.6.947"},{"key":"refg12\/ref12","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.073122"},{"key":"refg13\/ref13","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2008.1024"},{"key":"refg14\/ref14","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2003.03873.x"},{"key":"refg15\/ref15","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.4.3.293"},{"key":"refg16\/ref16","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn324"},{"key":"refg17\/ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2005.04.061"},{"key":"refg18\/ref18","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201101-0093OC"},{"key":"refg19\/ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.11.016"},{"key":"refg20\/ref20","doi-asserted-by":"crossref","DOI":"10.1016\/j.yjmcc.2007.03.646","volume":"42","author":"Khatib S.Y.","year":"2007","journal-title":"J. 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