title: Therapeutic effects of udenafil on pressure-overload cardiac hypertrophy.
abstract: This study was performed to determine whether the newly developed phosphodiesterase type 5 (PDE5) inhibitor udenafil had beneficial effects on pressure-overload cardiac hypertrophy. Pressure overload cardiac hypertrophy was created by using suprarenal aortic constriction (SAC) in male Sprague-Dawley rats. Rats were divided into three groups: sham (n=19), SAC (n=18) and SAC+udenafil (n=14) groups. Three-week periods of SAC provoked significant left ventricular (LV) hypertrophy. Udenafil was administered (20 mg kg(-1) PO, daily) between the 3rd and 20th weeks after SAC in the SAC+udenafil group. Udenafil improved the survival rate (log-rank P=0.012) and exercise capacity (maximal exercise duration at the 20th week after surgery: 448±54 s for the SAC+udenafil group versus 317±73 s for the SAC group, P<0.05) of the rats with SAC. Serial echocardiographic examinations showed that udenafil attenuated LV remodeling processes following SAC (mean LV end-diastolic dimension at the 20th week after surgery: 9.84±0.59 mm for SAC and 9.05±0.58 mm for SAC+udenafil group, P<0.05). Invasive hemodynamic studies showed that udenafil improved the LV performance. Udenafil-attenuated myocardial fibrosis and apoptosis. Udenafil also decreased myocardial matrix metalloproteinase-9 expression and augmented serum interleukin-10 concentration. Long-term udenafil use prevented cardiac remodeling and improved exercise capacity and survival in rats exposed to pressure-overload cardiac hypertrophy.
authors.affiliation: Boramae Medical Center, Seoul, South Korea.|Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hack-Lyoung
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.
authors.forename: Yong-Jin
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Sejong General Hospital, Bucheon, South Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.
authors.forename: Seung-Pyo
authors.initials: SP
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.
authors.forename: Hyung-Kwan
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Sohn
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.
authors.forename: Byung-Hee
authors.initials: BH
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.|Seoul National University Hospital, Seoul, South Korea.|Healthcare System Gangnam Center, Seoul, South Korea.
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Park
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D017079:Exercise Tolerance; D005355:Fibrosis / Q000517:prevention & control; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000188:drug therapy; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D016019:Survival Analysis; D014463:Ultrasonography; D000096926:Benzenesulfonamides
chemical_list: D000959:Antihypertensive Agents; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C572337:Mmp9 protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides
references.citation: Biopharm Drug Dispos. 2005 Oct;26(7):269-77
references.pmid: 15991256
references.citation: J Pharm Sci. 2003 Nov;92(11):2185-95
references.pmid: 14603504
references.citation: J Biol Chem. 2005 Apr 1;280(13):12944-55
references.pmid: 15668244
references.citation: Lancet. 2011 Aug 20;378(9792):704-12
references.pmid: 21856484
references.citation: Dig Liver Dis. 2015 Feb;47(2):144-50
references.pmid: 25483910
references.citation: Br J Clin Pharmacol. 2008 Jun;65(6):848-54
references.pmid: 18318773
references.citation: Int J Impot Res. 2009 Mar-Apr;21(2):122-8
references.pmid: 19194451
references.citation: Circulation. 2001 Jan 16;103(2):220-5
references.pmid: 11208680
references.citation: Br J Clin Pharmacol. 2009 Jul;68(1):43-6
references.pmid: 19660002
references.citation: Cardiovasc Res. 2000 May;46(2):214-24
references.pmid: 10773225
references.citation: Circulation. 2011 Jan 25;123(3):327-34
references.pmid: 21263005
references.citation: Hypertens Res. 2014 Jan;37(1):35-42
references.pmid: 24026041
references.citation: Annu Rev Immunol. 2001;19:683-765
references.pmid: 11244051
references.citation: Hypertens Res. 2014 Jan;37(1):43-9
references.pmid: 24089264
references.citation: Circulation. 2012 Mar 20;125(11):1390-401
references.pmid: 22319106
references.citation: N Engl J Med. 1992 Jan 9;326(2):90-4
references.pmid: 1309211
references.citation: Life Sci. 2006 Feb 9;78(11):1211-6
references.pmid: 16214180
references.citation: COPD. 2012 Aug;9(5):499-504
references.pmid: 22946546
references.citation: Circ Res. 1990 Mar;66(3):735-46
references.pmid: 2137728
references.citation: J Biomech. 2007;40(5):972-80
references.pmid: 16750211
references.citation: Circulation. 2003 Oct 28;108(17):2066-9
references.pmid: 14568893
references.citation: Circ Res. 2003 Apr 4;92(6):595-7
references.pmid: 12637371
references.citation: Arch Intern Med. 2002 Jun 24;162(12):1349-60
references.pmid: 12076233
references.citation: BMC Pharmacol. 2005 Apr 06;5:10
references.pmid: 15813973
references.citation: Trials. 2013 Jun 22;14:188
references.pmid: 23799908
references.citation: Front Biosci. 2005 May 01;10:1221-8
references.pmid: 15769620
references.citation: J Exp Med. 2007 Mar 19;204(3):657-66
references.pmid: 17339407
references.citation: Nat Med. 2005 Feb;11(2):214-22
references.pmid: 15665834
references.citation: Arch Pharm Res. 2002 Dec;25(6):873-8
references.pmid: 12510841
references.citation: Circulation. 2005 Oct 25;112(17):2642-9
references.pmid: 16246964
references.citation: Eur Heart J. 2003 Dec;24(24):2186-96
references.pmid: 14659770
references.citation: PLoS One. 2013;8(3):e58841
references.pmid: 23527037
references.citation: Circulation. 2005 Apr 5;111(13):1601-10
references.pmid: 15811867
references.citation: J Am Coll Cardiol. 2007 Nov 27;50(22):2136-44
references.pmid: 18036451
references.citation: Circulation. 2001 Sep 4;104(10):1147-52
references.pmid: 11535571