Abstract: TH-OR060

Pannexin 1 Channels in Renin Expressing Cells Regulate RAAS and Blood Pressure

Session Information

Category: Hypertension

  • 1103 Vascular Biology and Dysfunction

Authors

  • DeLalio, Leon, University of Virginia, Charlottesville, Virginia, United States
  • Masati, Ester, University of Virginia, Charlottesville, Virginia, United States
  • Le, Thu H., University of Virginia School of Medicine, Charlottesville, Virginia, United States
  • Barrett, Paula Q, University of Virginia, Charlottesville, Virginia, United States
  • Gomez, Roberto Ariel, University of Virginia, Charlottesville, Virginia, United States
  • Isakson, Brant, University of Virginia, Charlottesville, Virginia, United States
Background

The homeostatic regulation of blood pressure (BP) by renin lineage-cell differentiation in the renal vasculature and the adrenal zona glomerulosa (ZG) is crucial for controlling renin expression and aldosterone synthesis. In the renal vasculature, renin lineage cells respond to changes in blood pressure by differentiating and re-expressing a fetal renin gene program, termed recruitment. In the adrenal cortex, ZG cells of the renin lineage centripetally turnover, differentiating from an aldosterone synthetic program to a glucocorticoid synthetic one, thus maintaining steady state aldosterone production. The cellular signals coordinating these responses is unclear, but evidence from our lab posits a potential role for purinergic signaling mediated by Pannexin 1 channels. We hypothesized that Pannexin 1 (Px1) channels regulate purinergic communication and cell differentiation in the renal vasculature and adrenal ZG cells to maintain blood pressure homeostasis.

Methods

Blood pressure radiotelemtry, hormone specific RIA and ELISA, immunohistological staining, qPCR, and pressure myography.

Results

To test this hypothesis, we generated a novel renin cell Panx1 knockout mouse (Ren1-Px1 KO). At baseline, mice exhibit no differences in kidney size, morphology, or plasma renin concentration. However, KO mice have enhanced vasoconstriction responses and a significant elevation in aldosterone levels (1737 compared to 1172 pg/mL; p<0.5), which corresponded with aberrant ZG cell differentiation in the adrenal cortex. By radiotelemetry, Ren1-Px1 KO mice displayed increased baseline BP (110 compared to 100 mmHg; p<0.5). Lastly, we assessed renal renin dynamics in response to BP lowering with captopril. Ren1-Px1 KO mice retain adequate capacity to secrete renin at baseline, but fail to adequately upregulate renin expression in the juxtaglomerular afferent arteriole, determined by quantitative immunostaining, after BP lowering.

Conclusion

We conclude that loss of Panx1 from renin lineage cells causes activation of RAAS primarily by influencing differentiation responses in ZG cells, despite changes in renal renin dynamics. Thus, Pannxin 1 channels may regulate complex adrenal cell differentiation events important for long term BP control.

Funding

  • Other NIH Support