title: Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload.
abstract: Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy.
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Balázs Tamás
authors.initials: BT
authors.lastname: Németh
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Mátyás
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Oláh
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Lux
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Hidi
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Ruppert
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Dalma
authors.initials: D
authors.lastname: Kellermayer
authors.affiliation: Institute of Pathophysiology, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Kökény
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Im Neuenheimer Feld 110., 69210 Heidelberg, Germany.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015290:Second Messenger Systems / Q000187:drug effects*
chemical_list: D001565:Benzoates; C480588:BAY 58-2667; D006152:Cyclic GMP