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Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle

Author

Listed:
  • Ashenafi H. Betrie

    (The University of Melbourne
    The University of Melbourne
    Tianjin University, Tianjin; Center for Drug Development, Wannan Medical College)

  • James A. Brock

    (The University of Melbourne)

  • Osama F. Harraz

    (University of Vermont
    University of Vermont)

  • Ashley I. Bush

    (The University of Melbourne)

  • Guo-Wei He

    (Tianjin University, Tianjin; Center for Drug Development, Wannan Medical College)

  • Mark T. Nelson

    (University of Vermont
    University of Vermont
    University of Manchester)

  • James A. Angus

    (The University of Melbourne)

  • Christine E. Wright

    (The University of Melbourne)

  • Scott Ayton

    (The University of Melbourne)

Abstract

Zinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrate three mechanisms for zinc-induced vasorelaxation: (1) activation of transient receptor potential ankyrin 1 to increase calcitonin gene-related peptide signalling from perivascular sensory nerves; (2) enhancement of cyclooxygenase-sensitive vasodilatory prostanoid signalling in the endothelium; and (3) inhibition of voltage-gated calcium channels in the smooth muscle. These data introduce zinc as a new target for vascular therapeutics.

Suggested Citation

  • Ashenafi H. Betrie & James A. Brock & Osama F. Harraz & Ashley I. Bush & Guo-Wei He & Mark T. Nelson & James A. Angus & Christine E. Wright & Scott Ayton, 2021. "Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23198-6
    DOI: 10.1038/s41467-021-23198-6
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    Cited by:

    1. Sayaka Oda & Kazuhiro Nishiyama & Yuka Furumoto & Yohei Yamaguchi & Akiyuki Nishimura & Xiaokang Tang & Yuri Kato & Takuro Numaga-Tomita & Toshiyuki Kaneko & Supachoke Mangmool & Takuya Kuroda & Reish, 2022. "Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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