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

A, Mora; Andrade, de; Janussi, Sabrina; Gonçalves, Tiago Tomazini; Krikorian, K. S.; Priviero, Fernanda; Claudino, Mário A.

doi:10.1016/j.lfs.2021.120237

Cited by 4 publications

(3 citation statements)

References 60 publications

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“…The simultaneous application of L-NAME reversed the effects of tadalafil, while there were no significant changes in the case of vardenafil. This supports the hypothesis regarding the contribution of the L-arginin/NO system on the effects of tadalafil and suggests that there may be another endothelial pathway for vardenafil-induced vascular effects [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. It seems that tadalafil expresses its effects similarly to sildenafil, through the augmentation of NO synthase and cGMP levels, which points to the possibility that the cardiovascular dysfunctions that include decreased NOS activity may be alleviated by tadalafil treatment [ 30 , 31 ].…”

Section: Discussionsupporting

confidence: 86%

“…In one study, tadalafil decreased the levels of hydrogen peroxide, while in two others, sildenafil expressed the same effects on both the superoxide anion radical and hydrogen peroxide [ 21 , 22 , 23 ]. However, it should be taken into account that these studies were performed on men with erectile dysfunction and models with heart failure [ 24 , 25 , 26 , 27 ]. In both these cases, the basic antioxidant system was seriously damaged, which was not the case in our study.…”

Section: Discussionmentioning

confidence: 99%

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Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion

Krivokapic

Omarov²,

Živković

et al. 2023

Medicina

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Background and objectives: Taking into consideration the confirmed role of oxidative stress in ischemia/reperfusion injury and the insufficiency in knowledge regarding the phosphodiesterase 5 (PDE5)-mediated effects on the cardiovascular system, the aim of our study was to investigate the influence of two PDE5 inhibitors, tadalafil and vardenafil, with or without the addition of N(G)-nitro-L-arginine methyl ester (L-NAME), on oxidative stress markers, coronary flow and left ventricular function, both ex vivo and in vivo. Methods: This study included 74 male Wistar albino rats divided into two groups. In the first, 24 male Wistar rats were orally treated with tadalafil or vardenafil for four weeks in order to perform in vivo experiments. In the second, the hearts of 50 male Wistar albino were excised and perfused according to the Langendorff technique in order to perform ex vivo experiments. The hearts were perfused with tadalafil (10, 20, 50 and 200 nM), vardenafil (10, 20, 50 and 200 nM) and a combination of tadalafil/vardenafil and L-NAME (30 μM). The CF and oxidative stress markers, including nitrite bioaviability (NO2−), superoxide anion radical (O2−), and the index of lipid peroxidation, were measured in coronary effluent. Results: The L-arginin/NO system acts as the mediator in the tadalafil-induced effects on the cardiovascular system, while it seems that the vardenafil-induced increase in CF was not primarily induced by the NO system. Although tadalafil induced an increase in O2− in the two lowest doses, the general effects of both of the applied PDE5 inhibitors on oxidative stress were not significant. The ejection function was above 50% in both groups. Conclusions: Our results showed that both tadalafil and vardenafil improved the coronary perfusion of the myocardium and LV function by increasing the EF.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion

Krivokapic

Omarov²,

Živković

et al. 2023

Medicina

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“…Therefore, without these groups, it may be difficult to know if the results were from balanced effects or if the treatments prevented the negative effects of the obstruction. Previous studies demonstrated that NaHS and tadalafil treated control rats displayed similar responses in bladder function, inflammation and oxidative stress markers compared to control rats (32,33). The current use of a sulfide salt, NaHS is likely to be regarded as a limitation for the application of our study to urological practice, but numerous studies have revealed that H 2 S is effective on bladder function (5,34).…”

Section: B Amentioning

confidence: 88%

Co-administration of sodium hydrosulfide and tadalafil modulates hypoxia and oxidative stress on bladder dysfunction in a rat model of bladder outlet obstruction

et al. 2022

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Purpose: This study aimed to assess the possible healing effect of combination treatment with a hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS) plus tadalafil on partial bladder outlet obstruction (PBOO)-induced bladder dysfunction. Materials and Methods: A total of 75 male Sprague-Dawley rats aged 10-wk and 300-350g were divided into five groups; control; PBOO; PBOO+NaHS (5.6mg/kg/day, i.p., 6-wk); PBOO+tadalafil (2mg/kg/day, oral, 6-wk) and PBOO+NaHS+tadalafil. PBOO was created by partial urethral ligation. 6 weeks after obstruction, the in vitro contractile responses of the detrusor muscle and Western blotting, H2S and malondialdehyde assay were performed in bladder tissues. Results: There was an increase in bladder weight(p<0.001) and a decrease in contractile responses to KCl (p<0.001), carbachol (p<0.01), electrical field stimulation (p<0.05) and ATP (p<0.001) in the detrusor smooth muscle of obstructed rats which was normalized after the combination treatment. Cystathionine γ-lyase and cystathionine γ-synthase, and nuclear factor kappa B protein levels did not significantly differ among groups. The obstruction induced decrement in 3-mercaptopyruvate sulfur transferase protein expression(p<0.001) and H2S levels(p<0.01) as well as increment in protein expressions of neuronal nitric oxide synthase (NO, p<0.001), endothelial NOS (p<0.05), inducible NOS(p<0.001), hypoxia-inducible factor 1-alpha (p<0.01), and malondialdehyde levels (p<0.01), when combined treatment entirely normalized. Conclusions: Combination therapy has beneficial effects on bladder dysfunction via regulating both H2S and nitric oxide pathways as well as downregulation of oxidative stress and hypoxia. The synergistic effect of H2S and nitric oxide is likely to modulate bladder function, which supports the combined therapy for enhancing clinical outcomes in men with BPH/LUTS.

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Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development

Luo¹,

Zhao²,

He³

et al. 2023

Biomedicine & Pharmacotherapy

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

Cited by 4 publications

References 60 publications

Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion

Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion

Co-administration of sodium hydrosulfide and tadalafil modulates hypoxia and oxidative stress on bladder dysfunction in a rat model of bladder outlet obstruction

Research progress of indole-fused derivatives as allosteric modulators: Opportunities for drug development

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