Renal denervation attenuates pressure overload-induced cardiac remodelling in rats with biphasic regulation of autophagy

Aim: This study aimed to investigate effects of renal denervation (RDN) on pressure overload-induced cardiac remodelling in rats and the related mechanisms.

Methods: Adult male Sprague-Dawley rats underwent transverse aortic constriction (TAC) to generate cardiac remodelling. RDN was performed 1 week after TAC. The Animals were divided into four groups: control group, TAC group, TAC+RDN group and control+RDN group. Rats in all groups were studied at 3 and 10 weeks after TAC respectively. Echocardiography and histology were used to evaluate cardiac function and pathological changes. TUNEL staining and western blotting were used to assess Apoptosis. Western blotting and transmission electron microscopy (TEM) were used to evaluate Autophagy.

Results: Three weeks after TAC, the TAC rats exhibited cardiac hypertrophy with normal cardiac function and no myocardial interstitial fibrosis or Apoptosis, accompanied by a lower LC3 II level and fewer autophagic vacuoles in the left ventricles, both in the presence and absence of chloroquine (CQ), indicating suppressed Autophagy at this stage. RDN ameliorated these pathological changes and attenuated the decrease in Autophagy. Ten weeks after TAC, the TAC rats had decreased cardiac function, obvious cardiac interstitial fibrosis and Apoptosis, with increased Autophagy. RDN prevented these pathological changes, coincident with attenuation of increased Autophagy.

Conclusion: Autophagy was suppressed at the early stage but activated at the late stage of TAC-induced cardiac remodelling. RDN attenuated the pathological changes of TAC rats, accompanied by attenuation of the changes in Autophagy. Thus, RDN ameliorated TAC-induced cardiac remodelling partially associated with biphasic modulation of Autophagy.