Kidney Week

Abstract: FR-PO196

Decreased Blood Pressure in Vascular Smooth Muscle Specific ATP2B1 Overexpressing Mice

Session Information

• Vascular Biology and Dysfunction
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Hypertension

• 1103 Vascular Biology and Dysfunction

Authors

• Ehara, Yosuke, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan

Yosuke Ehara,

• Hirawa, Nobuhito, Yokohama City University Medical Center, Yokohama, Japan

Nobuhito Hirawa,

• Fujiwara, Akira, Yokohama City University Medical Center, Yokohama, Japan

Akira Fujiwara,

• Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan

Kouichi Tamura,

Background

We reported the association between high blood pressure and ATP2B1 gene polymorphisms in Japanese population through Millennium Genome Project. ATP2B1 is a gene encoding plasma membrane calcium ATPase 1 (PMCA1), which is known to be expressed throughout the body. PMCA1 plays a role of discharging Ca²⁺ from the inside of the cell to the outside of the cell, and strictly adjusts the intracellular Ca²⁺ concentration. In subsequent studies we reported that ATP2B1 vascular smooth muscle-specific knockout mice exhibit hypertension and are associated with elevated Ca²⁺ concentrations in vascular smooth muscle cells(VSMC). However, there were no data concerning the effects of ATP2B1 overexpressions. Thus, we generate the vascular smooth muscle-specific ATP2B1 overexpressing mice, and investigate the effects of ATP2B1 on blood pressure.

Methods

ATP2B1 vascular smooth muscle-specific overexpressing mice (Tg^ATP2B1) was prepared by microinjection method using transgelin (sm22) as a promoter. The expression level of ATP2B1 was confirmed in the aorta. Birth rate, body weight, organ weight, biochemical findings of Tg^ATP2B1 were compared with the wild type mice. We compared the blood pressure and heart rate by the tail cuff method and telemetry method in the two groups.

Results

There was no significant change in birth rate, body weight (Tg^ATP2B1 versus WT : 27.1 ± 0.6 versus 28.1 ± 1.1 ; P:0.46), organ weight. Serum calcium concentrations (8.83 ± 0.13 versus 8.78 ± 0.12 ; P:0.78) of Tg^ATP2B1 were also the same with those of wild mice. Although there was no difference in heart rate, a significant decrease in blood pressure was observed in Tg^ATP2B1 mice using tail-cuff methods (99.4 ± 2.73 versus 108.4 ± 2.72 ; P:0.03). By radio-telemetry methods, the blood pressure of Tg^ATP2B1 were decreased throughout 24hrs. The blood pressure variabilities were not altered by the over-expression of ATP2B1 in vascular smooth muscle cells.

Conclusion

Vascular smooth muscle-specific ATP2B1 overexpressing mice exhibited lower blood pressure compared to those of wild mice by the tail cuff method and the telemetry method. ATP2B1 over-expression in VSMC might decrease the intra-celular Ca²⁺ concentrations and decrease the contractilities in Tg^ATP2B1 mice.