Spironolactone enhances the beneficial effect of aliskiren on cardiac structural and electrical remodeling in TGR(mRen2)27 rats

Abstract

Objective: To investigate the influence of simultaneous administration of spironolactone (20 mg/kg per day, intraperitoneal (i.p.)) and aliskiren (50 mg/kg per day, i.p.) for a period of eight weeks on cardiac remodeling in TGR(mRen2)27 rats. Methods: Echocardiographic and electrophysiological and histological methods were used to determine the influence of spironolactone and aliskiren on cardiac remodeling. Results: 1) the beneficial effect of aliskiren on SBP was enhanced by simultaneous administration of spironolactone; 2) echocardiographic studies showed that the left ventricle diameter (LVD), the left ventricle end diastolic volume (LVEDV) and the left ventricle posterior wall thickness (LVPW) were significantly reduced by the combination of both drugs when compared with aliskiren alone; 3) the ejection fraction was also increased; 4) histological studies indicated a greater decline in perivascular and interstitial fibrosis when both drugs were used; 5) the decrease of electrical remodeling of the left ventricle caused by aliskiren was further reduced by simultaneous administration of spironolactone; 6) the cardiac refractoriness increased by aliskiren was further incremented by spironolactone. Spironolactone (20 mg/kg per day) alone increased the ejection fraction and reduced LVD, LVEDV and LVPW but its effect was smaller than that achieved with the combination spironolactone plus aliskiren. Conclusion:The combination of an aldosterone inhibitor with a direct renin inhibitor proved to be of greater benefit for cardiac structural and electrical remodeling in this experimental model of hypertension than aliskiren alone.

Clinical Perspectives and Fundamental Aspects of Local Cardiovascular and Renal Renin-Angiotensin Systems

“…Recent observations indicated that spironolactone enhances the beneficial effect of aliskiren on cardiac structural and electrical remodeling in TGR(mRen2)27 rats (122) and that chronic administration of eplerenone to the failing heart reduces the cardiac effect of Ang II on inward calcium current through a decline in AT1 receptor level at the surface cell membrane (91). Because AT1 receptor is a mechanosensor involved in cardiac remodeling, it is reasonable to think that part of the beneficial effect of spironolactone in the failing heart is related to a smaller sensitivity of cardiac muscle to mechanical stress.…”

The use of aliskiren as an antifibrotic drug in experimental models: A systematic review

“…Furthermore, it reduces ventricular mass according to the ALLAY study, which revealed that ALI is as effective as losartan in the reduction of hypertrophied ventricular mass in hypertensive patients with BMI >25 kg/m 2 (Solomon et al, 2009). Myocardial thickness was reduced, according to many articles that analyzed the effects of ALI (Table 1) in cardiac experimental models (Campbell et al, 2011;De Mello, 2015;Fischer et al, 2008;Takamura et al, 2016;Weng et al, 2014;Yamada et al, 2016).…”