Acute intracerebroventricular injection of chemerin-9 increases systemic blood pressure through activating sympathetic nerves via CMKLR1 in brain

Abstract

Chemerin is an adipocytokine involved in inflammation and lipid metabolism via G protein-coupled receptor, chemokine-like receptor (CMKLR)1. Since the important nuclei regulating pressure (BP) exist in the brain, we examined the effects of acute intracerebroventricular (i.c.v.) injection of chemerin-9 on systemic BP and explored underlying mechanisms. We examined the effects of acute i.c.v. injection of chemerin-9 (10 nmol/head) on systemic BP by a carotid cannulation method in the control or CMKLR1 small interfering (si) RNA-treated Wistar rats (0.04 nmol, 3 days, i.c.v.). We examined protein expression of CMKLR1 around brain ventricles by Western blotting. We examined the effects of acute i.c.v. injection of chemerin-9 on serum adrenaline by a high performance liquid chromatography. In the control siRNA-treated rats, chemerin-9 significantly increased mean BP, which reached a peak at 2 to 4 min after injection. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the mean BP. Protein expression of CMKLR1 specifically in subfornical organ (SFO) and paraventricular nucleus (PVN) from the CMKLR1 siRNA-treated rats decreased compared with the control siRNA-treated rats. In the control siRNA-treated rats, chemerin-9 increased serum adrenaline level. On the other hand, in the CMKLR1 siRNA-treated rats, chemerin-9 did not affect the serum adrenaline level. Further, pretreatment with prazosin, an α-adrenaline receptor blocker, significantly prevented the pressor responses induced by chemerin-9. In summary, we for the first time demonstrated that chemerin-9 stimulates the sympathetic nerves via CMKLR1 perhaps expressed in SFO and PVN, which leads to an increase in systemic BP.

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Acknowledgments

This study was supported by JSPS KAKENHI Grant Number 17H03918 and Kitasato University Research Grant.

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Correspondence to Hideyuki Yamawaki.

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Yamamoto, A., Matsumoto, K., Hori, K. et al. Acute intracerebroventricular injection of chemerin-9 increases systemic blood pressure through activating sympathetic nerves via CMKLR1 in brain. Pflugers Arch - Eur J Physiol 472, 673–681 (2020). https://doi.org/10.1007/s00424-020-02391-4

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Keywords

  • Adipocytokine
  • Blood pressure
  • Brain
  • Intracerebroventricular injection
  • Sympathetic nerve