Role of Musclin in the Pathogenesis of Hypertension in Rat

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.

Telmisartan is effective to ameliorate metabolic syndrome in rat model – a preclinical report

“…Body weight was monitored weekly. BP was determined at week 9 (before drug treatment) and week 13 (the end of 4-week periods of the drug treatment) using the tail-cuff method with a sphygmomanometer (Muromachi Kikai Co., Ltd., Tokyo, Japan) 33…”

C-Type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature

“…Further evidence in favour of a role of NPR-C in the pathogenesis of hypertension was published in a study investigating the effects of the endogenous secretory peptide musclin (also known as osteocrin). Musclin is a competitive ligand at NPR-C and the infusion of musclin increases systolic blood pressure in vivo [87]. Gene expression levels of musclin are elevated in spontaneously hypertensive rats (SHR) and the administration of anti-musclin antibodies reduces blood pressure in these animals, intimating that interference with NP binding at NPR-C by musclin may contribute to the hypertensive state of these animals [87].…”

“…Musclin is a competitive ligand at NPR-C and the infusion of musclin increases systolic blood pressure in vivo [87]. Gene expression levels of musclin are elevated in spontaneously hypertensive rats (SHR) and the administration of anti-musclin antibodies reduces blood pressure in these animals, intimating that interference with NP binding at NPR-C by musclin may contribute to the hypertensive state of these animals [87]. However, contrary to this research is a study showing that the infusion of musclin (osteocrin) lowers blood pressure in mice, an effect that is absent in NPR-A KO animals, suggesting that an increase in circulating levels of ANP and/or BNP due to the blockade of peptide clearance by NPR-C accounts for this response [88].…”

Muscle as a paracrine and endocrine organ

“…Thus, skeletal muscle-dependent release of FSTL1 could have multiple therapeutic effects on the cardiovascular system. Other myokines reported to have salutary effects on the cardiovascular system include fibroblast growth factor 21 (FGF21), musclin, and apelin which have been linked to cardioprotection, protection from atherosclerosis and control of blood pressure respectively[15,43–46]. However, again, future studies are required to determine if skeletal muscle is a major contributor to the circulating levels of these factors.…”