Limits...
Role of musclin in the pathogenesis of hypertension in rat.

Li YX, Cheng KC, Asakawa A, Kato I, Sato Y, Amitani H, Kawamura N, Cheng JT, Inui A - PLoS ONE (2013)

Bottom Line: Thus, musclin is found to bind with the natriuretic peptide clearance receptors.Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody.Taken together, these results suggest that musclin is involved in blood pressure regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Changes of blood pressure by musclin antibodies in SHR.(A) Changes in the blood pressure of SHR or (B) WKY observed after intravenous injection of anti-musclin antibodies. Anti-musclin antibodies at the indicated dilutions were injected into rats. The blood pressure at 0 min was taken as basal control. Blood pressure values are expressed as mean ± SEM (n = 8). *Significance compared with that treated with antibody 1:5000 at the same time point and # significance compared with that at 0 minute using 2-way repeated measures ANOVA for each strain.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3733923&req=5

pone-0072004-g008: Changes of blood pressure by musclin antibodies in SHR.(A) Changes in the blood pressure of SHR or (B) WKY observed after intravenous injection of anti-musclin antibodies. Anti-musclin antibodies at the indicated dilutions were injected into rats. The blood pressure at 0 min was taken as basal control. Blood pressure values are expressed as mean ± SEM (n = 8). *Significance compared with that treated with antibody 1:5000 at the same time point and # significance compared with that at 0 minute using 2-way repeated measures ANOVA for each strain.

Mentions: The anti-musclin antibody FL-133 was used to investigate the effect of musclin on blood pressure in SHR. The solutions of FL-133 at 1:5000, 1:1000, or 1:500 dilutions were administered to SHR via intravenous injection. FL-133 at 1:5000 dilution did not induce a change in the blood pressure, and it was therefore taken as the control. Differently from the control, FL-133 at 1:1000 dilution decreased the blood pressure in SHR at 10 min after the injection (P < 0.05, n = 8) (Figure 8A). FL-133 at 1:500 dilution lowered the blood pressure in SHR more markedly at 10 min and 20 min after the injection (P < 0.01, n = 8). However, the blood pressure recovered within 30 min after the injection of FL-133 in all concentrations. In contrast, similar treatment with FL-133 at the same dilutions failed to modify the blood pressure in WKY (Figure 8B). Otherwise, treatment with control IgG at 1:500 dilution made no change of blood pressure in SHR (201.6 ± 10.9 mmHg; P>0.05, n=8).


Role of musclin in the pathogenesis of hypertension in rat.

Li YX, Cheng KC, Asakawa A, Kato I, Sato Y, Amitani H, Kawamura N, Cheng JT, Inui A - PLoS ONE (2013)

Changes of blood pressure by musclin antibodies in SHR.(A) Changes in the blood pressure of SHR or (B) WKY observed after intravenous injection of anti-musclin antibodies. Anti-musclin antibodies at the indicated dilutions were injected into rats. The blood pressure at 0 min was taken as basal control. Blood pressure values are expressed as mean ± SEM (n = 8). *Significance compared with that treated with antibody 1:5000 at the same time point and # significance compared with that at 0 minute using 2-way repeated measures ANOVA for each strain.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3733923&req=5

pone-0072004-g008: Changes of blood pressure by musclin antibodies in SHR.(A) Changes in the blood pressure of SHR or (B) WKY observed after intravenous injection of anti-musclin antibodies. Anti-musclin antibodies at the indicated dilutions were injected into rats. The blood pressure at 0 min was taken as basal control. Blood pressure values are expressed as mean ± SEM (n = 8). *Significance compared with that treated with antibody 1:5000 at the same time point and # significance compared with that at 0 minute using 2-way repeated measures ANOVA for each strain.
Mentions: The anti-musclin antibody FL-133 was used to investigate the effect of musclin on blood pressure in SHR. The solutions of FL-133 at 1:5000, 1:1000, or 1:500 dilutions were administered to SHR via intravenous injection. FL-133 at 1:5000 dilution did not induce a change in the blood pressure, and it was therefore taken as the control. Differently from the control, FL-133 at 1:1000 dilution decreased the blood pressure in SHR at 10 min after the injection (P < 0.05, n = 8) (Figure 8A). FL-133 at 1:500 dilution lowered the blood pressure in SHR more markedly at 10 min and 20 min after the injection (P < 0.01, n = 8). However, the blood pressure recovered within 30 min after the injection of FL-133 in all concentrations. In contrast, similar treatment with FL-133 at the same dilutions failed to modify the blood pressure in WKY (Figure 8B). Otherwise, treatment with control IgG at 1:500 dilution made no change of blood pressure in SHR (201.6 ± 10.9 mmHg; P>0.05, n=8).

Bottom Line: Thus, musclin is found to bind with the natriuretic peptide clearance receptors.Moreover, this contraction was reduced by blockade of natriuretic peptide receptor C using the ab14355 antibody.Taken together, these results suggest that musclin is involved in blood pressure regulation.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus