{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:10:29Z","timestamp":1787242229285,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T00:00:00Z","timestamp":1384387200000},"content-version":"vor","delay-in-days":0,"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":[[2013,12]]},"abstract":"\n Background and Purpose<\/jats:title>\n \n Inhibition of the cGMP\u2010specific phosphodiesterase 5 (\n PDE5<\/jats:styled-content>\n ) exerts profound beneficial effects on failing hearts. However, the mechanisms underlying the therapeutic effects of\n PDE5<\/jats:styled-content>\n inhibition on heart failure are unclear. The purpose of this study was to investigate whether\n PDE5<\/jats:styled-content>\n inhibition decreases endoplasmic reticulum (\n ER<\/jats:styled-content>\n ) stress, a key event in heart failure.\n <\/jats:p>\n <\/jats:sec>\n \n Experimental Approach<\/jats:title>\n \n Heart failure was induced by isoprenaline s.c. injection in\n S<\/jats:styled-content>\n prague\u2013\n D<\/jats:styled-content>\n awley rats and transverse aortic constriction (\n TAC<\/jats:styled-content>\n ) in mice. PDE5 was inhibited with sildenafil. Heart function was detected by invasive pressure\u2013volume analysis and echocardiography.\n ER<\/jats:styled-content>\n stress markers were analysed by Western blotting. Apoptosis was measured by flow cytometric analysis.\n <\/jats:p>\n <\/jats:sec>\n \n Key Results<\/jats:title>\n \n PDE5<\/jats:styled-content>\n inhibition markedly attenuated isoprenaline\u2010induced and\n TAC<\/jats:styled-content>\n \u2010induced cardiac hypertrophy and dysfunction, and reduced\n ER<\/jats:styled-content>\n stress and apoptosis. Further,\n PDE5<\/jats:styled-content>\n inhibition with sildenafil largely prevented\n ER<\/jats:styled-content>\n stress and reduced apoptosis in isoprenaline\u2010 or thapsigargin\u2010treated cardiomyocytes.\n PKG<\/jats:styled-content>\n inhibition markedly prevented the protective effects of sildenafil\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n . To further understand the mechanism of the effect of\n PDE5<\/jats:styled-content>\n inhibition on\n ER<\/jats:styled-content>\n stress, we demonstrated that\n PDE5<\/jats:styled-content>\n inhibitor increased sarco\u2010(endo)\u2010plasmic reticulum\n \n \n Ca\n 2+<\/jats:sup>\n <\/jats:roman>\n <\/jats:styled-content>\n \u2010\n ATPase<\/jats:styled-content>\n activity via phosphorylation of phospholamban at Ser\n 16<\/jats:sup>\n . This may contribute to the attenuation of\n ER<\/jats:styled-content>\n stress induced by\n PDE5<\/jats:styled-content>\n inhibition.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Implications<\/jats:title>\n \n These results suggest that\n PDE5<\/jats:styled-content>\n inhibition can attenuate\n ER<\/jats:styled-content>\n stress and improve cardiac function\n in vivo<\/jats:italic>\n and\n in vitro<\/jats:italic>\n . Suppression of\n ER<\/jats:styled-content>\n stress by inhibiting\n PDE5<\/jats:styled-content>\n may contribute to the therapeutic effects on heart failure.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bph.12346","type":"journal-article","created":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T07:24:47Z","timestamp":1377156287000},"page":"1396-1409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Chronic inhibition of cGMP\u2010specific phosphodiesterase 5 suppresses endoplasmic reticulum stress in heart failure"],"prefix":"10.1111","volume":"170","author":[{"given":"Wei","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Gene Therapy Center Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanlu","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gene Therapy Center Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhejun","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gene Therapy Center Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Gene Therapy Center Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan 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