Renin–angiotensin–aldosterone system blockade with telmisartan prevents the decline in cardiac contractility orchiectomy-dependent in SHR: role of PPAR-γ activation

Abstract The present study aimed to investigate the beneficial role of AT1 receptor blockade and PPAR-γ activation in preventing cardiac contractile changes in hypertensive animals (SHR) with testosterone deficiency. Rats were divided into a control group (sham), orchiectomized (OCT), orchiectomized that received telmisartan (OCT + Tel) or telmisartan plus PPAR-γ antagonist (OCT + Tel + BADGE). After 8 weeks, contractility of isolated papillary muscles was evaluated. The OCT group showed a reduction in the contraction force, avoided in the OCT + Tel and Tel + BADGE groups. Post-pause potentiation (PPP) was similar in the Sham, OCT and OCT + Tel group, suggesting prevention of sarcoplasmic reticulum activity. In contrast, PPP in the OCT + Tel + BADGE group decreased. The reduction in response to calcium or isoproterenol in the OCT group was prevented in the OCT + Tel and Tel + BADGE group. The influx of calcium, assessed indirectly, although it was similar in the OCT and Sham groups, increased both in the OCT + Tel groups and in the OCT + Tel + BADGE groups. SERCA2a protein expression was increased in the OCT group, which was avoided in the OCT + Tel and Tel + BADGE group. NCX expression was increased in the Tel + BADGE group compared to OCT + Tel and sham. Our results suggest that AT1 receptor blockade with telmisartan prevents compromised papillary muscle contractility in SHR. Moreover, it has been shown that the activation of PPAR-γ adds benefits to the inhibition of renin-angiotensin system with telmisartan in preventing harmful effects on the contractility of hypertensive rats with testosterone deficiency.