Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
 free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
 free
 free
 
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve
Pubget Overpricing |  
lüll
alpha-Melanocyte-stimulating hormone regulates vascular NO availability and protects against endothelial dysfunction Rinne P; Nordlund W; Heinonen I; Penttinen AM; Saraste A; Ruohonen ST; Makela S; Vahatalo L; Kaipio K; Cai M; Hruby VJ; Ruohonen S; Savontaus ECardiovasc Res 2013[Feb]; 97 (2): 360-8AIMS: 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.|Acetylcholine/pharmacology[MESH]|Animals[MESH]|Cells, Cultured[MESH]|Coronary Circulation/drug effects[MESH]|Endothelium, Vascular/*physiology[MESH]|Humans[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|Nitric Oxide Synthase Type III/physiology[MESH]|Nitric Oxide/*physiology[MESH]|Receptor, Melanocortin, Type 1/physiology[MESH]|Signal Transduction/physiology[MESH]|Vasodilation/drug effects[MESH]|alpha-MSH/*pharmacology[MESH] |
