α-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction

Petteri Rinne, Wendy Nordlund, Ilkka Heinonen, Anna Maija Penttinen, Antti Saraste, Suvi T. Ruohonen, Satu Mäkelä, Laura Vähätalo, Katja Kaipio, Minying Cai, Victor J. Hruby, Saku Ruohonen, Eriika Savontaus

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Aimsα-Melanocyte-stimulating hormone (α-MSH), derived from the precursor molecule pro-opiomelanocortin, exerts potent anti-inflammatory actions in the vasculature, but its role in circulatory regulation remains unclear. Therefore, we sought to investigate whether α-MSH could regulate the local control of blood vessel tone.Methods and resultsUsing in vivo and ex vivo methods to assess vascular reactivity, we found that α-MSH improved endothelium-dependent vasodilatation in the mouse aorta and coronary circulation without directly contracting or relaxing blood vessels. α-MSH promoted vasodilatation by enhancing endothelial nitric oxide (NO) formation and by improving sensitivity to endothelium-independent blood vessel relaxation. Using cultured human endothelial cells to elucidate the involved molecular mechanisms, we show that α-MSH increased the expression and phosphorylation of endothelial NO synthase in these cells. The observed effects were regulated by melanocortin 1 (MC1) receptors expressed in the endothelium. In keeping with the vascular protective role of α-MSH, in vivo treatment with stable analogues of α-MSH ameliorated endothelial dysfunction associated with aging and diet-induced obesity in mice.ConclusionThe present study identifies α-MSH and endothelial MC1 receptors as a new signalling pathway contributing to the regulation of NO availability and vascular function. These findings suggest applicability of α-MSH analogues for therapeutic use in pathological conditions that are characterized by vascular dysfunction.

Original languageEnglish (US)
Pages (from-to)360-368
Number of pages9
JournalCardiovascular research
Volume97
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • Endothelial function
  • Endothelial nitric oxide synthase
  • Melanocortin
  • Nitric oxide
  • Vasodilation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Rinne, P., Nordlund, W., Heinonen, I., Penttinen, A. M., Saraste, A., Ruohonen, S. T., Mäkelä, S., Vähätalo, L., Kaipio, K., Cai, M., Hruby, V. J., Ruohonen, S., & Savontaus, E. (2013). α-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction. Cardiovascular research, 97(2), 360-368. https://doi.org/10.1093/cvr/cvs335