Kidney Week

Abstract: SA-PO1002

Proximal Tubule Angiotensin II Type 1 Receptor-Associated Protein Does Not Influence Angiotensin-Dependent Hypertension

Session Information

• Hypertension and CVD: Mechanisms - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Wakui, Hiromichi, Yokohama City University, Kanagawa, Yokohama city, Japan

Hiromichi Wakui,

• Kinguchi, Sho, Yokohama City University, Kanagawa, Yokohama city, Japan

Sho Kinguchi,

• Yamaji, Takahiro, Yokohama city unversity, Yokohama City, Japan

Takahiro Yamaji,

• Uneda, Kazushi, Yokohama City University, Kanagawa, Yokohama city, Japan

Kazushi Uneda,

• Urate, Shingo, Yokohama City University Graduate School of Medicine, Kanazawa-Ku, KANAGAWA, Japan

Shingo Urate,

• Haruhara, Kotaro, The Jikei University School of Medcine, Tokyo, Japan

Kotaro Haruhara,

• Ohki, Kohji, Yokohama City University School of Medicine, Yokohama City, Japan

Kohji Ohki,

• Kobayashi, Ryu, Yokohama City University Graduate School of Medicine, Kanazawa-Ku, KANAGAWA, Japan

Ryu Kobayashi,

• Azushima, Kengo, Yokohama City University, Kanagawa, Yokohama city, Japan

Kengo Azushima,

• Toya, Yoshiyuki, Yokohama City University, Kanagawa, Yokohama city, Japan

Yoshiyuki Toya,

• Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Kanazawa-Ku, KANAGAWA, Japan

Kouichi Tamura,

Background

The activation of renal angiotensin II (Ang II) type 1 receptor (AT1R) can evoke excessive sodium retention, resulting in hypertension when inappropriately stimulated. The AT1R-associated protein (ATRAP) has been identified as the specific binding protein of the C-terminal domain of AT1R, and functions as an endogenous inhibitor that suppresses AT1R hyper-activation at local tissue sites. We previously reported that systemic ATRAP-knockout mice (ATRAP-KO) exhibited an exacerbation of Ang II-induced hypertension, concomitant with an increase in sodium retention, compared wild-type mice (WT). We here report a functional role of proximal tubule ATRAP in angiotensin-dependent hypertension using proximal tubule-specific ATRAP-knockout (PT-KO) mice.

Methods

In the present study, we generated PT-KO mice for the first time by the Cre/loxP system using Pepck-Cre. We next compared blood pressure in response to Ang II (1000ng/kg/min) treatment in wild-type littermate control (LC) and PT-KO mice. Since cardiac hypertrophy is closely associated with the blood pressure elevation, we further examined heart weight/body weight ratio in PT-KO and LC mice.

Results

The ATRAP mRNA expression in the proximal tubules of the PT-KO mice was decreased by approximately 80% compared with LC mice, estimated by laser capture microdissection method. Ang II infusion for 2 weeks significantly and similarly increased systolic blood pressure in both PT-KO and LC mice. Ang II infusion for 2 weeks significantly increased heart weight/body weight ratio in both PT-KO and LC mice to the same extent.

Conclusion

These results indicate that ATRAP deficiency in proximal nephron does not influence angiotensin-dependent hypertension in vivo.