Musclin is a novel skeletal muscle-derived secretory factor found in the signal 
sequence trap of mouse skeletal muscle cDNAs. Musclin possesses a region 
homologous to the natriuretic peptide family. Thus, musclin is found to bind 
with the natriuretic peptide clearance receptors. However, the role of musclin 
in vascular regulation remains unclear. In this study, we aim to investigate the 
direct effect of musclin on vascular tone and to analyze its role in 
hypertension using the spontaneously hypertensive rats (SHR). In aortic strips 
isolated from SHR, musclin induced contractions in a dose-dependent manner. We 
found that the musclin-induced vasoconstriction was more marked in SHR than in 
normal rats (WKY). Moreover, this contraction was reduced by blockade of 
natriuretic peptide receptor C using the ab14355 antibody. Therefore, mediation 
of the natriuretic peptide receptor in musclin-induced vasoconstriction can be 
considered. In addition, similar to the natriuretic peptide receptor, expression 
of the musclin gene in blood vessels was higher in SHR than in WKY. Injection of 
musclin markedly increased the blood pressure in rats that can be inhibited by 
anti-musclin antibodies. Musclin-induced vasoconstriction was more pronounced in 
SHR than in WKY as in its expression. Taken together, these results suggest that 
musclin is involved in blood pressure regulation. The higher expression of 
musclin in hypertension indicates that musclin could be used as a new target for 
the treatment of hypertension in the future.