{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:08:27Z","timestamp":1790935707305,"version":"4.1.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Molecular and Cellular Cardiology"],"published-print":{"date-parts":[[2009,4]]},"DOI":"10.1016\/j.yjmcc.2008.12.008","type":"journal-article","created":{"date-parts":[[2008,12,30]],"date-time":"2008-12-30T05:54:49Z","timestamp":1230616489000},"page":"560-567","source":"Crossref","is-referenced-by-count":45,"title":["Pressure-overload magnitude-dependence of the anti-hypertrophic efficacy of PDE5A inhibition"],"prefix":"10.1016","volume":"46","author":[{"given":"Takahiro","family":"Nagayama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norimichi","family":"Koitabashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djahida","family":"Bedja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen L.","family":"Gabrielson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Takimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Kass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.yjmcc.2008.12.008_bib1","doi-asserted-by":"crossref","first-page":"e69","DOI":"10.1161\/CIRCULATIONAHA.106.179918","article-title":"Heart disease and stroke statistics\u20142007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"115","author":"Rosamond","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nature06798","article-title":"Tackling heart failure in the twenty-first century","volume":"451","author":"Mudd","year":"2008","journal-title":"Nature"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nrd2193","article-title":"Small-molecule therapies for cardiac hypertrophy: moving beneath the cell surface","volume":"6","author":"McKinsey","year":"2007","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib4","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1161\/01.RES.0000100390.68771.CC","article-title":"Cyclic GMP-dependent protein kinases and the cardiovascular system: insights from genetically modified mice","volume":"93","author":"Feil","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib5","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.cardiores.2007.02.031","article-title":"Phosphodiesterase regulation of nitric oxide signaling","volume":"75","author":"Kass","year":"2007","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib6","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nrd2030","article-title":"Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond","volume":"5","author":"Ghofrani","year":"2006","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib7","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1161\/CIRCRESAHA.107.162511","article-title":"Phosphodiesterase type 5: expanding roles in cardiovascular regulation","volume":"101","author":"Kass","year":"2007","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib8","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/nm1175","article-title":"Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy","volume":"11","author":"Takimoto","year":"2005","journal-title":"Nat Med"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib9","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1124\/jpet.108.137422","article-title":"Sustained soluble guanylate cyclase stimulation offsets nitric-oxide synthase inhibition to restore acute cardiac modulation by sildenafil","volume":"326","author":"Nagayama","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib10","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1161\/01.RES.0000152262.22968.72","article-title":"cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism","volume":"96","author":"Takimoto","year":"2005","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib11","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1161\/CIRCULATIONAHA.106.643536","article-title":"Compartmentalization of cardiac beta-adrenergic inotropy modulation by phosphodiesterase type 5","volume":"115","author":"Takimoto","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib12","doi-asserted-by":"crossref","DOI":"10.1152\/ajpheart.ajpheart.91438.2007","article-title":"Sildenafil (Viagra) attenuates ischemic cardiomyopathy and improves left ventricular function in mice","author":"Salloum","year":"2008","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib13","doi-asserted-by":"crossref","first-page":"12944","DOI":"10.1074\/jbc.M404706200","article-title":"Phosphodiesterase-5 inhibitor sildenafil preconditions adult cardiac myocytes against necrosis and apoptosis. Essential role of nitric oxide signaling","volume":"280","author":"Das","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib14","doi-asserted-by":"crossref","DOI":"10.1016\/j.cellsig.2008.08.012","article-title":"Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes","author":"Zhang","year":"2008","journal-title":"Cell Signal"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib15","doi-asserted-by":"crossref","first-page":"2642","DOI":"10.1161\/CIRCULATIONAHA.105.540500","article-title":"Sildenafil inhibits beta-adrenergic-stimulated cardiac contractility in humans","volume":"112","author":"Borlaug","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib16","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.jacc.2008.08.069","article-title":"Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy due to pressure-overload","volume":"53","author":"Nagayama","year":"2009","journal-title":"J Am Coll Cardiol"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib17","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/CIRCRESAHA.108.175133","article-title":"Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance","volume":"103","author":"Sayed","year":"2008","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib18","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1161\/hc4401.098432","article-title":"Upregulation of phosphodiesterase 1A1 expression is associated with the development of nitrate tolerance","volume":"104","author":"Kim","year":"2001","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ejphar.2008.05.009","article-title":"Prevention of nitroglycerin tolerance in vitro by T0156, a selective phosphodiesterase type 5 inhibitor","volume":"590","author":"Liu","year":"2008","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib20","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1124\/jpet.105.094763","article-title":"Inhibition of phosphodiesterase 5 selectively reverses nitrate tolerance in the venous circulation","volume":"317","author":"MacPherson","year":"2006","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib21","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1161\/01.RES.0000246118.98832.04","article-title":"Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases","volume":"99","author":"Fischmeister","year":"2006","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib22","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1161\/CIRCULATIONAHA.105.599241","article-title":"Cyclic guanosine monophosphate compartmentation in rat cardiac myocytes","volume":"113","author":"Castro","year":"2006","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib23","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1172\/JCI17061","article-title":"Pressure-independent cardiac hypertrophy in mice with cardiomyocyte-restricted inactivation of the atrial natriuretic peptide receptor guanylyl cyclase-A","volume":"111","author":"Holtwick","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib24","doi-asserted-by":"crossref","first-page":"47694","DOI":"10.1074\/jbc.M309661200","article-title":"Expression of constitutively active guanylate cyclase in cardiomyocytes inhibits the hypertrophic effects of isoproterenol and aortic constriction on mouse hearts","volume":"278","author":"Zahabi","year":"2003","journal-title":"J Biol Chem"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib25","doi-asserted-by":"crossref","first-page":"11363","DOI":"10.1073\/pnas.162100799","article-title":"Inhibition of calcineurin-NFAT hypertrophy signaling by cGMP-dependent protein kinase type I in cardiac myocytes","volume":"99","author":"Fiedler","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib26","doi-asserted-by":"crossref","unstructured":"Takimoto E, Koitabashi N, Hsu S, Ketner EA, Zhang M, Nagayama T, et al. RGS2 mediates cardiac compensation to pressure-overload and anti-hypertrophic effects of PDE5 inhibition. J Clin Invest,53(2) in press, doi:10.1172\/JCI35620.","DOI":"10.1172\/JCI35620"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib27","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1038\/nm958","article-title":"Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure","volume":"9","author":"Tang","year":"2003","journal-title":"Nat Med"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib28","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.yjmcc.2006.04.003","article-title":"Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation","volume":"41","author":"Hao","year":"2006","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib29","article-title":"RGS2 mediates cardiac compensation to pressure-overload and anti-hypertrophic effects of PDE5 inhibition","author":"Takimoto","year":"2008","journal-title":"J Clin Invest"},{"issue":"Suppl II","key":"10.1016\/j.yjmcc.2008.12.008_bib30","first-page":"II","article-title":"PDE5A inhibition suppresses maladaptive but not physiological cardiac hypertrophy","volume":"114","author":"Mulhearn","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib31","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1073\/pnas.231619298","article-title":"Activated glycogen synthase-3 beta suppresses cardiac hypertrophy in vivo","volume":"99","author":"Antos","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib32","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1172\/JCI19906","article-title":"Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore","volume":"113","author":"Juhaszova","year":"2004","journal-title":"J Clin Invest"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib33","doi-asserted-by":"crossref","first-page":"29572","DOI":"10.1074\/jbc.M801547200","article-title":"Protein kinase G dependent cardioprotective mechanism of phosphodiesterase-5 inhibition involves phosphorylation of ERK and GSK3beta","volume":"283","author":"Das","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1161\/01.RES.0000065442.64694.9F","article-title":"Reengineering inducible cardiac-specific transgenesis with an attenuated myosin heavy chain promoter","volume":"92","author":"Sanbe","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib35","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1161\/CIRCRESAHA.107.160614","article-title":"Inhibition of glycogen synthase kinase 3beta during heart failure is protective","volume":"101","author":"Hirotani","year":"2007","journal-title":"Circ Res"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib36","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1161\/CIRCULATIONAHA.106.659763","article-title":"Cardiac structure and ventricular-vascular function in persons with heart failure and preserved ejection fraction from Olmsted County, Minnesota","volume":"115","author":"Lam","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.yjmcc.2008.12.008_bib37","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jacc.2006.08.050","article-title":"Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling\/dysfunction","volume":"49","author":"Melenovsky","year":"2007","journal-title":"J Am Coll Cardiol"}],"container-title":["Journal of Molecular and Cellular Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282808014491?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022282808014491?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,5,16]],"date-time":"2019-05-16T17:23:31Z","timestamp":1558027411000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022282808014491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["S0022282808014491"],"URL":"https:\/\/doi.org\/10.1016\/j.yjmcc.2008.12.008","relation":{},"ISSN":["0022-2828"],"issn-type":[{"value":"0022-2828","type":"print"}],"subject":[],"published":{"date-parts":[[2009,4]]}}}