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Updated: Mar 12, 2026
Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
Published on: June 29, 2014
Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload
Balázs Tamás Németh1, Csaba Mátyás1, Attila Oláh1
1Heart and Vascular Center, Semmelweis University, Városmajor u. 68., 1122 Budapest, Hungary.
Insights
Cinaciguat, a soluble guanylate cyclase activator, prevented pathological cardiac hypertrophy in rats with pressure overload. This suggests enhancing cyclic guanosine monophosphate (cGMP) signaling may offer a new therapeutic strategy for heart hypertrophy.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Pathological cardiac hypertrophy results from chronic heart pressure overload.
- Elevated intracellular cyclic guanosine monophosphate (cGMP) levels may inhibit this hypertrophy.
Purpose of the Study:
- To investigate the effects of chronic soluble guanylate cyclase (sGC) activation by Cinaciguat on pressure overload-induced cardiac hypertrophy in rats.
Main Methods:
- Male Wistar rats underwent abdominal aortic banding (AAB) to induce pressure overload.
- Animals received daily oral administration of Cinaciguat (10 mg/kg) or placebo for six weeks.
- Sham-operated rats served as controls.
Main Results:
- AAB induced pathological cardiac hypertrophy, shown by increased heart weight, cardiomyocyte size, collagen, and apoptosis.
- Cinaciguat treatment attenuated these hypertrophy features without altering blood pressure.
- Cinaciguat also normalized functional changes, including contractility, in AAB rats.
Conclusions:
- Chronic enhancement of cGMP signaling via pharmacological sGC activation may prevent pathological cardiac hypertrophy.
- Cinaciguat demonstrates potential as a novel therapeutic approach for preventing heart hypertrophy.
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.
