Abstract: FR-PO196

Decreased Blood Pressure in Vascular Smooth Muscle Specific ATP2B1 Overexpressing Mice

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • Ehara, Yosuke, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan
  • Hirawa, Nobuhito, Yokohama City University Medical Center, Yokohama, Japan
  • Fujiwara, Akira, Yokohama City University Medical Center, Yokohama, Japan
  • Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan
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 (TgATP2B1) 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 TgATP2B1 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 (TgATP2B1 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 TgATP2B1 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 TgATP2B1 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 TgATP2B1 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 TgATP2B1 mice.