Tadalafil treatment improves cardiac, renal and lower urinary tract dysfunctions in rats with heart failure

Author(s)

Mora, Aline Goncalves ; Andrade, Douglas Rafael ; Janussi, Sabrina C. ; Goncalves, Tiago Tomazini ; Krikorian, Karla ; Priviero, Fernanda B. M. ; Claudino, Mario Angelo

• Document type: Journal article
• Source: Life Sciences; v. 289, p. 10-pg., 2022-01-15.

Abstract

Tadalafil, a phosphodiesterase-5 (PDE5) inhibitor, shown to exert a protection to heart failure (HF) associated damage or lower urinary tract symptoms (LUTS). Thus, we investigated the contribution of tadalafil chronic treatment in the alterations of LUTS in HF rats. Male rats were subjected to aortocaval fistula model for HF induction. Echocardiography, cystometric, renal function and redox cell balance, as well as concentration response curves to carbachol, KCl, ATP and frequency-response curves to electrical field stimulation (EFS) were evaluated in Sham, HF, Tadalafil and HF-Tadalafil (12 weeks endpoint) groups. HF group to present increased in left-ventricle (LV) mass and in LV end -diastolic-and LV end-systolic volume, with a decreased ejection fraction. Tadalafil treatment was able to decrease in hypertrophy and improve the LV function restoring cardiac function. For micturition function (in vivo), HF animals shown an increase in basal pressure, threshold pressure, no-voiding contractions and decreased bladder capacity, being that the tadalafil treatment restored the cystometric parameters. Contractile mechanism response (in vitro) to carbachol, KCl, ATP and EFS in the detrusor muscles (DM) were increased in the HF group, when compared to Sham group. However, tadalafil treatment restored the DM hypercontractility in the HF animals. Moreover, renal function as well as the oxidative mechanism was impaired in the HF animals, and the tadalafil treatment improved all renal and oxidative parameters in HF group. Our data shown that tadalafil has potential as multi-therapeutic drug and may be used as a pharmacological strategy for the treatment of cardiovascular, renal and urinary dysfunctions associated with HF. (AU)

• FAPESP's process: 11/21095-4 - Morphofunctional and molecular study of erectile function and lower urinary tract in rats with chronic heart failure: evaluation of the NO-sGC-cGMP signaling pathway
• Grantee: Mário Angelo Claudino
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 19/27841-1 - To evaluate the multitherapeutic action of AT1 receptor antagonist associated with neprilysin inhibitor in the treatment of cardiovascular and urogenital dysfunction in heart failure rats
• Grantee: Mário Angelo Claudino
• Support Opportunities: Regular Research Grants