Laboratory of Multidisciplinary Research, São Francisco University Medical School, Bragança Paulista, SP, Brazil.
Cardiovascular Translational Research Center and Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC, USA.
Life Sci. 2022 Jan 15;289:120237. doi: 10.1016/j.lfs.2021.120237. Epub 2021 Dec 16.
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.
他达拉非是一种磷酸二酯酶 5(PDE5)抑制剂,已被证明可对心力衰竭(HF)相关损伤或下尿路症状(LUTS)发挥保护作用。因此,我们研究了他达拉非慢性治疗对 HF 大鼠 LUTS 改变的贡献。雄性大鼠接受腔静脉瘘模型以诱导 HF。在 Sham、HF、Tadalafil 和 HF-Tadalafil(12 周终点)组中评估了超声心动图、膀胱测压、肾功能和氧化还原细胞平衡,以及对卡巴胆碱、氯化钾、ATP 的浓度-反应曲线和对电场刺激(EFS)的频率-反应曲线。HF 组表现出左心室(LV)质量增加,LV 舒张末期和 LV 收缩末期容积增加,射血分数降低。他达拉非治疗能够减少肥大并改善 LV 功能,恢复心脏功能。对于排尿功能(体内),HF 动物表现出基础压力、阈值压力、无排空收缩增加和膀胱容量减少,而他达拉非治疗恢复了膀胱测压参数。在逼尿肌(DM)中对 carbachol、KCl、ATP 和 EFS 的收缩机制反应(体外)在 HF 组中增加,与 Sham 组相比。然而,他达拉非治疗恢复了 HF 动物的 DM 高收缩性。此外,HF 动物的肾功能和氧化机制受损,他达拉非治疗改善了 HF 组的所有肾功能和氧化参数。我们的数据表明,他达拉非具有作为多治疗药物的潜力,可作为治疗与 HF 相关的心血管、肾脏和泌尿系统功能障碍的药理学策略。