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The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: Possible role of calcineurin and p38

Show simple item record Zeidan A. Siam A. Al Kaabba A. Mohammad M. Khatib S.
dc.contributor.editor Sep-2012 2017-09-07T06:59:57Z 2017-09-07T06:59:57Z 2012
dc.identifier 10.1139/Y2012-098
dc.identifier.issn 00084212
dc.description.abstract 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± 0.18 mm from 4.6 ± 0.13 mm (p andlt; 0.05), which regressed after treatment with either sildenafil or or-donafil to 5.1 ± 0.1 mm and 4.8 ± 0.2 mm, respectively (p andlt; 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131percent ± 3percent of the control value, which was associated with significant increment in ERK1-2 to 143percent ± 5percent of the control value (p andlt; 0.05). Ordonafil and sildenafil decreased cell surface area to 95percent ± 3percent and 90percent ± 1percent of the control value, respectively. Both drugs decreased ERK1-2 to 88percent ± 4percent of the control value. Calcineurin activity was significantly decreased after 1 h of treatment with 0.1 mg·L-1 ordonafil (1.15 ± 0.05, p andlt; 0.05). For sildenafil (0.1 mg·L-1), calcineurin activity significantly decreased only after 24 h of incubation (22percent). Also p38 activation was attenuated by ordonafil and sildenafil (0.1 mg·L-1). 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.
dc.format.extent Pages: (1247-1255)
dc.language English
dc.publisher OTTAWA
dc.relation.ispartof Publication Name: Canadian Journal of Physiology and Pharmacology; Publication Year: 2012; Volume: 90; no. 9; Pages: (1247-1255);
dc.source Scopus
dc.title The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: Possible role of calcineurin and p38
dc.type Article
dc.contributor.affiliation Zeidan, A., Department of Anatomy, Cell Biology, and Physiological Sciences, American University of Beirut, Beirut, Lebanon
dc.contributor.affiliation Siam, A., Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
dc.contributor.affiliation Al Kaabba, A., Faculty of Medicine, King Fahad Medical City, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11525, Saudi Arabia
dc.contributor.affiliation Mohammad, M., Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
dc.contributor.affiliation Khatib, S., Department of Physiology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
dc.contributor.authorAddress Khatib, S.; Faculty of Medicine, King Fahad Medical City, King Saud Bin Abdulaziz University for Health Sciences, P.O. Box 59046, Riyadh 11525, Saudi Arabia; email:
dc.contributor.authorCorporate University: American University of Beirut Medical Center; Faculty: Faculty of Medicine; Department: Anatomy, Cell Biology and Physiological Sciences;
dc.contributor.authorDepartment Anatomy, Cell Biology and Physiological Sciences
dc.contributor.faculty Faculty of Medicine
dc.contributor.authorInitials Zeidan, A
dc.contributor.authorInitials Siam, A
dc.contributor.authorInitials Al Kaabba, A
dc.contributor.authorInitials Mohammad, M
dc.contributor.authorInitials Khatib, S
dc.contributor.authorReprintAddress Khatib, S (reprint author), King Saud Bin Abdulaziz Univ Hlth Sci, Fac Med, King Fahad Med City, POB 59046, Riyadh 11525, Saudi Arabia.
dc.contributor.authorUniversity American University of Beirut Medical Center
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dc.description.citedCount 2
dc.description.citedTotWOSCount 4
dc.description.citedWOSCount 3
dc.format.extentCount 9
dc.identifier.coden CJPPA
dc.identifier.pubmedID 22913522
dc.identifier.scopusID 84865426471
dc.publisher.address 1200 MONTREAL ROAD, BUILDING M-55, OTTAWA, ON K1A 0R6, CANADA
dc.relation.ispartOfISOAbbr Can. J. Physiol. Pharmacol.
dc.relation.ispartOfIssue 9
dc.relation.ispartofPubTitle Canadian Journal of Physiology and Pharmacology
dc.relation.ispartofPubTitleAbbr Can. J. Physiol. Pharmacol.
dc.relation.ispartOfVolume 90
dc.source.ID WOS:000308152200011
dc.type.publication Journal
dc.subject.otherAuthKeyword Calcineurin
dc.subject.otherAuthKeyword Heart
dc.subject.otherAuthKeyword Hypertrophy
dc.subject.otherAuthKeyword Mapk
dc.subject.otherAuthKeyword Ordonafil
dc.subject.otherAuthKeyword Phosphodiesterase 5 inhibitor
dc.subject.otherAuthKeyword Sildenafil
dc.subject.otherChemCAS calcineurin, 137951-12-3
dc.subject.otherChemCAS mitogen activated protein kinase 1, 137632-08-7
dc.subject.otherChemCAS mitogen activated protein kinase 3, 137632-07-6
dc.subject.otherChemCAS n(g) nitroarginine methyl ester, 50903-99-6
dc.subject.otherChemCAS phenylephrine, 532-38-7, 59-42-7, 61-76-7
dc.subject.otherChemCAS sildenafil, 139755-83-2
dc.subject.otherChemCAS Calcineurin,
dc.subject.otherChemCAS JPM8 compound
dc.subject.otherChemCAS NG-Nitroarginine Methyl Ester, V55S2QJN2X
dc.subject.otherChemCAS Phosphodiesterase 5 Inhibitors
dc.subject.otherChemCAS Piperazines
dc.subject.otherChemCAS Purines
dc.subject.otherChemCAS Sulfones
dc.subject.otherChemCAS p38 Mitogen-Activated Protein Kinases,
dc.subject.otherChemCAS sildenafil, 3M7OB98Y7H
dc.subject.otherIndex calcineurin
dc.subject.otherIndex mitogen activated protein kinase 1
dc.subject.otherIndex mitogen activated protein kinase 3
dc.subject.otherIndex mitogen activated protein kinase p38
dc.subject.otherIndex n(g) nitroarginine methyl ester
dc.subject.otherIndex ordonafil
dc.subject.otherIndex phenylephrine
dc.subject.otherIndex phosphodiesterase V inhibitor
dc.subject.otherIndex sildenafil
dc.subject.otherIndex unclassified drug
dc.subject.otherIndex animal cell
dc.subject.otherIndex animal experiment
dc.subject.otherIndex animal model
dc.subject.otherIndex animal tissue
dc.subject.otherIndex article
dc.subject.otherIndex cell size
dc.subject.otherIndex cell surface
dc.subject.otherIndex controlled study
dc.subject.otherIndex drug effect
dc.subject.otherIndex drug mechanism
dc.subject.otherIndex enzyme activity
dc.subject.otherIndex enzyme inhibition
dc.subject.otherIndex experimental rabbit
dc.subject.otherIndex female
dc.subject.otherIndex heart left ventricle hypertrophy
dc.subject.otherIndex heart muscle cell
dc.subject.otherIndex male
dc.subject.otherIndex nonhuman
dc.subject.otherIndex priority journal
dc.subject.otherIndex protein synthesis inhibition
dc.subject.otherIndex rat
dc.subject.otherIndex signal transduction
dc.subject.otherIndex Animals
dc.subject.otherIndex Calcineurin
dc.subject.otherIndex Cardiomegaly
dc.subject.otherIndex Cell Size
dc.subject.otherIndex Female
dc.subject.otherIndex Male
dc.subject.otherIndex Myocytes, Cardiac
dc.subject.otherIndex NG-Nitroarginine Methyl Ester
dc.subject.otherIndex p38 Mitogen-Activated Protein Kinases
dc.subject.otherIndex Phosphodiesterase 5 Inhibitors
dc.subject.otherIndex Piperazines
dc.subject.otherIndex Purines
dc.subject.otherIndex Rabbits
dc.subject.otherIndex Rats
dc.subject.otherIndex Rats, Sprague-Dawley
dc.subject.otherIndex Sulfones
dc.subject.otherKeywordPlus NITRIC-OXIDE
dc.subject.otherKeywordPlus VENTRICULAR MYOCYTES
dc.subject.otherKeywordPlus PRESSURE-OVERLOAD
dc.subject.otherKeywordPlus MUSCLE-CELLS
dc.subject.otherKeywordPlus RATS
dc.subject.otherKeywordPlus KINASE
dc.subject.otherKeywordPlus ACTIVATION
dc.subject.otherKeywordPlus VARDENAFIL
dc.subject.otherWOS Pharmacology and Pharmacy
dc.subject.otherWOS Physiology

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