Deficiency of T-type voltage-gated calcium channels results in attenuated weight gain and improved endothelium-dependent dilatation of resistance vessels induced by a high-fat diet in mice

Kristoffer Rosenstand, Kenneth Andersen, Rasmus Terp, Peter Gennemark, Ditte Gry Ellman, Anna Reznichenko, Kate Lykke Lambertsen, Paul M Vanhoutte, Pernille B. Lærkegaard Hansen, Per Svenningsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The deletion of T-type Ca v3.1 channels may reduce high-fat diet (HFD)-induced weight gain, which correlates positively with obesity and endothelial dysfunction. Therefore, experiments were designed to study the involvement of T-type Ca v3.1 channels in HFD-induced endothelial dysfunction in mice. Wildtype (WT) and Ca v3.1 −/− mice were fed either a normal diet (ND) or an HFD for 8 weeks. Body composition was assessed, and thoracic aortae and mesenteric arteries were harvested for myography to assess endothelium-dependent responses. Changes in intracellular calcium were measured by fluorescence imaging, and behavior was assessed with the open-field test. Ca v3.1 −/− mice had attenuated HFD-induced weight gain and lower total fat mass compared with WT mice. Ca v3.1 −/− mice on an HFD had reduced plasma cholesterol levels compared with WT mice on the same diet. Increased feeding efficiency, independent of food intake, was observed in WT mice on an HFD compared with an ND, but no difference in feeding efficiency between diets was observed for Ca v3.1 −/− mice. Nitric oxide-dependent dilatation was increased in mesenteric arteries of Ca v3.1 −/− mice compared with WT mice on an HFD, with no difference observed in aortae. No differences in mouse locomotor activity were observed between the experimental groups. Mice on an HFD lacking T-type channels have reduced weight gain, lower total cholesterol levels, and increased dilatation of resistance vessels compared with WT mice on an HFD, suggesting that Ca v3.1 deletion protects against endothelial dysfunction in resistance vessels but not in large conduit vessels.

Original languageEnglish
JournalJournal of Physiology and Biochemistry
Volume76
Issue number1
Pages (from-to)135-145
ISSN1138-7548
DOIs
Publication statusPublished - 3. Feb 2020

Keywords

  • Calcium
  • Endothelium
  • Ion channels
  • Obesity

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