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Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 2, pp 355–365 | Cite as

Deletion of T-type calcium channels Cav3.1 or Cav3.2 attenuates endothelial dysfunction in aging mice

  • Anne D. Thuesen
  • Kenneth Andersen
  • Kristina S. Lyngsø
  • Mark Burton
  • Charlotte Brasch-Andersen
  • Paul M. Vanhoutte
  • Pernille B. L. HansenEmail author
Molecular and Cellular Mechanisms of Disease
Part of the following topical collections:
  1. Molecular and cellular mechanisms of disease

Abstract

Impairment of endothelial function with aging is accompanied by reduced nitric oxide (NO) production. T-type Cav3.1 channels augment nitric oxide and co-localize with eNOS. Therefore, the hypothesis was that T-type channels contribute to the endothelial dysfunction of aging. Endothelial function was determined in mesenteric arteries (perfusion) and aortae (isometric contraction) of young and old wild-type (WT), Cav3.1, and Cav3.2 knockout mice. NO production was measured by fluorescence imaging in mesenteric arteries. With age, endothelium-dependent subsequent dilatation (following depolarization with KCl) of mesenteric arteries was diminished in the arteries of WT mice, unchanged in Cav3.2−/− preparations but increased in those of Cav3.1−/− mice. NO synthase inhibition abolished the subsequent dilatation in mesenteric arteries and acetylcholine-induced relaxations in aortae. NO levels were significantly reduced in mesenteric arteries of old compared to young WT mice. In Cav3.1−/− and Cav3.2−/− preparations, NO levels increased significantly with age. Relaxations to acetylcholine were significantly smaller in the aortae of old compared to young WT mice, while such responses were comparable in preparations of young and old Cav3.1−/− and Cav3.2−/− mice. The expression of Cav3.1 was significantly reduced in aortae from aged compared to young WT mice. The level of phosphorylated eNOS was significantly increased in aortae from aged Cav3.1−/− mice. In conclusion, T-type calcium channel-deficient mice develop less age-dependent endothelial dysfunction. Changes in NO levels are involved in this phenomenon in WT and Cav3.1−/− mice. These findings suggest that T-type channels play an important role in age-induced endothelial dysfunction.

Keywords

Endothelial dysfunction NO T-type calcium channels Vasodilatation 

Notes

Acknowledgements

We would like to thank Vivi Monrad and Mie Rytz for expert technical assistance. Also, we thank Hee-Sup Shin, Center for Cognition and Sociality, Korea, for the Cav3.1−/− mice and Philippe Lory, University de Montpellier, France.

Funding

This work was supported by grants from the Danish Medical Research Council (11-107552), The Danish Heart Foundation (11-04-R84-A3492-22663), and Novo Nordic Foundation (13273).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

424_2017_2068_MOESM1_ESM.docx (18 kb)
ESM 1 (DOCX 18 kb)
424_2017_2068_MOESM2_ESM.pptx (278 kb)
ESM 2 (PPTX 278 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Anne D. Thuesen
    • 1
  • Kenneth Andersen
    • 1
  • Kristina S. Lyngsø
    • 1
  • Mark Burton
    • 3
  • Charlotte Brasch-Andersen
    • 3
  • Paul M. Vanhoutte
    • 2
  • Pernille B. L. Hansen
    • 1
    • 4
    Email author
  1. 1.Cardiovascular and Renal ResearchUniversity of Southern DenmarkOdense CDenmark
  2. 2.State Key Laboratory for Biopharmaceutical Technology and Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of MedicineUniversity of Hong KongHong KongChina
  3. 3.Department of Clinical GeneticOdense University HospitalOdenseDenmark
  4. 4.Cardiovascular and Metabolic Disease Innovative MedicinesAstraZenecaGothenburgSweden

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