Kidney Week

Abstract: SA-PO848

Tadalafil Treatment Attenuates Renal Dysfunction in Hypertensive Model Independent of Blood Pressure Lowering

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Tomita, Natsumi, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Natsumi Tomita,

• Hotta, Yuji, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Yuji Hotta,

• Naiki-Ito, Aya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Aya Naiki-Ito,

• Kataoka, Tomoya, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Tomoya Kataoka,

• Maeda, Yasuhiro, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Yasuhiro Maeda,

• Takahashi, Satoru, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan

Satoru Takahashi,

• Kimura, Kazunori, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan

Kazunori Kimura,

Background

Recently, phosphodiesterase 5 inhibitor (PDE5i) reportedly has renoprotective effects, which may be due to blood pressure (BP) lowering by PDE5i. Here, we assessed if the renopretective effect of tadalafil, a PDE5i, depends on its BP lowering using salt-sensitive hypertension rats.

Methods

Dahl salt-sensitive rats were divided into 4 groups (n=5-7): normal salt (NS), high salt (8 % NaCl included in diet; HS), low-dose (1 mg/kg/day, p.o; TL), and high-dose tadalafil treatment (10 mg/kg/day, p.o; TH). SCre, proteinuria, and BP were evaluated at 0 and 8 weeks. PAS staining and αSMA immunohistochemistry were performed. mRNA level of PAI1, which is reported to increase αSMA expression, was evaluated.

Results

In the HS, BP significantly increased at 8 weeks. The TH showed attenuated BP elevation. However, the TL showed BP elevation similar to the HS (Fig.1A). Proteinuria and SCre levels, which markedly increased in the HS at 8 weeks, were suppressed in the TH and TL (Fig.1B,C). PAS staining showed severe glomerulosclerosis in the HS and was prevented in the TH and TL (Fig. 2A). αSMA-positive area significantly increased in the HS and decreased in the TH and TL (Fig. 2B). PAI1 mRNA level was significantly upregurated in the HS. Tadalafil treatment dose-dependantly decreased PAI1 mRNA level.

Conclusion

Tadalafil treatment could prevent decline of the renal function independently of BP lowering. This effect might be associated with suppression of PAI1.

Fig.1 Variations of mean blood pressure (A), SCre (B), and Urinary protein (C) in each groups (n=5-7). Turkey’s test. *P<0.05,**P<0.01 vs. NS, ^# P<0.05, ^##P<0.01vs. HS.

Fig.2 Histopathological assessment; glomerulosclerosis index (A) and αSMA positive area (B). (n=4-6). Turkey’s test. *P<0.01