Abstract

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.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Simon Bulley

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Carlos Fernández-Peña

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Raquibul Hasan

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. M Dennis Leo

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Padmapriya Muralidharan

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Charles E Mackay

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kirk W Evanson

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Luiz Moreira-Junior

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Alejandro Mata-Daboin

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Sarah K Burris

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Qian Wang

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Korah P Kuruvilla

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Jonathan H Jaggar

    Department of Physiology, University of Tennessee Health Science Center, Memphis, United States
    For correspondence
    jjaggar@uthsc.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1505-3335

Funding

National Heart, Lung, and Blood Institute (HL67061)

  • Jonathan H Jaggar

National Heart, Lung, and Blood Institute (HL133256)

  • Jonathan H Jaggar

National Heart, Lung, and Blood Institute (HL137745)

  • Jonathan H Jaggar

American Heart Association (16SDG27460007)

  • Simon Bulley

American Heart Association (15SDG22680019)

  • M Dennis Leo

American Heart Association (16POST30960010)

  • Raquibul Hasan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Kenton Jon Swartz, National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to an approved institutional animal care and use committee (IACUC) protocol (#17-068.0) of the University of Tennessee. Every effort was made to minimize suffering.

Version history

  1. Received: October 5, 2018
  2. Accepted: November 22, 2018
  3. Accepted Manuscript published: December 4, 2018 (version 1)
  4. Version of Record published: December 5, 2018 (version 2)
  5. Version of Record updated: October 30, 2019 (version 3)
  6. Version of Record updated: June 30, 2020 (version 4)

Copyright

© 2018, Bulley et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,435
    views
  • 380
    downloads
  • 43
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Simon Bulley
  2. Carlos Fernández-Peña
  3. Raquibul Hasan
  4. M Dennis Leo
  5. Padmapriya Muralidharan
  6. Charles E Mackay
  7. Kirk W Evanson
  8. Luiz Moreira-Junior
  9. Alejandro Mata-Daboin
  10. Sarah K Burris
  11. Qian Wang
  12. Korah P Kuruvilla
  13. Jonathan H Jaggar
(2018)
Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure
eLife 7:e42628.
https://doi.org/10.7554/eLife.42628

Share this article

https://doi.org/10.7554/eLife.42628

Further reading

    1. Neuroscience
    Zahra Ghasemahmad, Aaron Mrvelj ... Jeffrey J Wenstrup
    Research Article

    The basolateral amygdala (BLA), a brain center of emotional expression, contributes to acoustic communication by first interpreting the meaning of social sounds in the context of the listener’s internal state, then organizing the appropriate behavioral responses. We propose that modulatory neurochemicals such as acetylcholine (ACh) and dopamine (DA) provide internal-state signals to the BLA while an animal listens to social vocalizations. We tested this in a vocal playback experiment utilizing highly affective vocal sequences associated with either mating or restraint, then sampled and analyzed fluids within the BLA for a broad range of neurochemicals and observed behavioral responses of adult male and female mice. In male mice, playback of restraint vocalizations increased ACh release and usually decreased DA release, while playback of mating sequences evoked the opposite neurochemical release patterns. In non-estrus female mice, patterns of ACh and DA release with mating playback were similar to males. Estrus females, however, showed increased ACh, associated with vigilance, as well as increased DA, associated with reward-seeking. Experimental groups that showed increased ACh release also showed the largest increases in an aversive behavior. These neurochemical release patterns and several behavioral responses depended on a single prior experience with the mating and restraint behaviors. Our results support a model in which ACh and DA provide contextual information to sound analyzing BLA neurons that modulate their output to downstream brain regions controlling behavioral responses to social vocalizations.