Kidney Week

Abstract: SA-PO1090

Chronic Treatment with Tadalafil Prevented Renal Dysfunction and Hypertension Caused by High Salt Intake and Preserved Serum SDF-1α Levels in Dahl Salt-Sensitive Rats

Session Information

• Hypertension: Basic and Experimental - Treatment and Mechanisms
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1102 Hypertension: Basic and Experimental - Renal Causes and Consequences

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

Phosphodiesterase inhibitors (PDE5is) are reported to prevent renal damage and/or blood pressure (BP) elevation in an ischemic-reperfusion model. It is uncertain whether PDE5is are effective against salt sensitive hypertension; thus, we investigated the effects of a PDE5i, tadalafil, on hypertension and renal dysfunction induced by high salt intake using an animal model.

Methods

Eight-week-old male Dahl salt-sensitive rats were divided into three groups (n=6); normal salt (NS), high salt (8% NaCl-included diet; HS), and high salt and tadalafil treatment (10 mg/kg/day, p.o; Tad). Blood urea nitrogen, serum creatinine (SCre), proteinuria, and BP were evaluated at 0, 4, and 8 weeks. The kidney was extracted at 8 weeks and PAS staining was performed. Serum stromal cell-derived factor 1 (SDF-1)-α level, which is associated with the repair of vascular endothelial injury, was also evaluated at the 8 week timepoint.

Results

BP and proteinuria significantly increased in the HS group (P<0.01), while tadalafil treatment attenuated proteinuria and BP elevation at 8 weeks (P<0.01 vs. HS) (Fig.1). While SCre did not increase in the Tad group, it increased in the HS group (P<0.05) at 8 weeks. Glomerulosclerosis and atherosclerosis in the kidney also increased in the HS group (P<0.01), although they were suppressed in the Tad group (P<0.01 vs. HS). Serum SDF-1α level significantly decreased (P<0.01) in the HS group and normalized in the Tad group (P<0.05 vs. HS).

Conclusion

Tadalafil may be an effective treatment for salt-sensitive hypertension, atherosclerosis, and renal dysfunction and maintains SDF-1α level.

Fig.1 Variations in systolic blood pressure (A) and urinary protein to creatinine ratio (B) in each group (n=6). ANOVA and Bonferroni-type multiple t-test. * P<0.01 vs. NS, # P<0.01 vs. HS