| First Author | Rinne P | Year | 2013 |
| Journal | Cardiovasc Res | Volume | 97 |
| Issue | 2 | Pages | 360-8 |
| PubMed ID | 23131503 | Mgi Jnum | J:210285 |
| Mgi Id | MGI:5569899 | Doi | 10.1093/cvr/cvs335 |
| Citation | Rinne P, et al. (2013) alpha-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction. Cardiovasc Res 97(2):360-8 |
| abstractText | AIMS: alpha-Melanocyte-stimulating hormone (alpha-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 alpha-MSH could regulate the local control of blood vessel tone. METHODS AND RESULTS: Using in vivo and ex vivo methods to assess vascular reactivity, we found that alpha-MSH improved endothelium-dependent vasodilatation in the mouse aorta and coronary circulation without directly contracting or relaxing blood vessels. alpha-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 alpha-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 alpha-MSH, in vivo treatment with stable analogues of alpha-MSH ameliorated endothelial dysfunction associated with aging and diet-induced obesity in mice. CONCLUSION: The present study identifies alpha-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 alpha-MSH analogues for therapeutic use in pathological conditions that are characterized by vascular dysfunction. |
