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Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

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 enzym...

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Main Authors: Németh, Balázs Tamás (Author) , Mátyás, Csaba (Author) , Oláh, Attila (Author) , Lux, Árpád (Author) , Hidi, László (Author) , Ruppert, Mihály (Author) , Kellermayer, Dalma (Author) , Kökény, Gábor (Author) , Szabó, Gábor (Author) , Merkely, Béla (Author) , Radovits, Tamás (Author)
Format: Article (Journal)
Language:English
Published: 17 November 2016
In: Scientific reports
Year: 2016, Volume: 6
ISSN:2045-2322
DOI:10.1038/srep37166
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/srep37166
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/srep37166
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Author Notes:Balázs Tamás Németh, Csaba Mátyás, Attila Oláh, Árpád Lux, László Hidi, Mihály Ruppert, Dalma Kellermayer, Gábor Kökény, Gábor Szabó, Béla Merkely & Tamás Radovits
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Summary: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.
Item Description:Gesehen am 09.10.2020
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/srep37166

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