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Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure.

eLife | 2018

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

Pubmed ID: 30511640 RIS Download

Associated grants

  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL137745
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK090868
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL067061
  • Agency: NHLBI NIH HHS, United States
    Id: HL137745
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL133256
  • Agency: NHLBI NIH HHS, United States
    Id: HL133256
  • Agency: NHLBI NIH HHS, United States
    Id: HL67061

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