Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 Bancho 35-1, Towada, Aomori 034-8628, Japan.
Int J Mol Sci. 2021 Oct 30;22(21):11812. doi: 10.3390/ijms222111812.
Adipocytokine chemerin is a biologically active molecule secreted from adipose tissue. Chemerin elicits a variety of functions via chemokine-like receptor 1 (CMKLR1). The cardiovascular center in brain that regulates blood pressure (BP) is involved in pathophysiology of systemic hypertension. Thus, we explored the roles of brain chemerin/CMKLR1 on regulation of BP in spontaneously hypertensive rats (SHR). For this aim, we examined effects of intracerebroventricular (i.c.v.) injection of CMKLR1 small interfering (si)RNA on both systemic BP as measured by tail cuff system and protein expression in paraventricular nucleus (PVN) of SHR as determined by Western blotting. We also examined both central and peripheral protein expression of chemerin by Western blotting. Systolic BP of SHR but not normotensive Wistar Kyoto rats (WKY) was decreased by CMKLR1 siRNA. The decrease of BP by CMKLR1 siRNA persisted for 3 days. Protein expression of CMKLR1 in PVN of SHR tended to be increased compared with WKY, which was suppressed by CMKLR1 siRNA. Protein expression of chemerin in brain, peripheral plasma, and adipose tissue was not different between WKY and SHR. In summary, we for the first time revealed that the increased protein expression of CMKLR1 in PVN is at least partly responsible for systemic hypertension in SHR.
脂肪细胞因子趋化素是一种由脂肪组织分泌的具有生物活性的分子。趋化素通过趋化因子样受体 1(CMKLR1)发挥多种功能。调节血压(BP)的大脑心血管中枢参与系统性高血压的病理生理学。因此,我们探索了脑趋化素/CMKLR1 在自发性高血压大鼠(SHR)血压调节中的作用。为此,我们通过尾套系统检测了脑室(i.c.v.)注射 CMKLR1 小干扰(si)RNA 对全身 BP 的影响,并通过 Western 印迹检测了 SHR 室旁核(PVN)中的蛋白表达。我们还通过 Western 印迹检测了趋化素的中枢和外周蛋白表达。与正常血压的 Wistar Kyoto 大鼠(WKY)相比,SHR 的收缩压(SBP)降低了,而 CMKLR1 siRNA 降低了 SHR 的 SBP。CMKLR1 siRNA 降低 BP 的作用持续了 3 天。与 WKY 相比,SHR 的 PVN 中 CMKLR1 的蛋白表达趋于增加,而 CMKLR1 siRNA 抑制了这种增加。WKY 和 SHR 之间的脑、外周血浆和脂肪组织中的趋化素蛋白表达没有差异。总之,我们首次揭示了 PVN 中 CMKLR1 蛋白表达的增加至少部分导致了 SHR 的全身高血压。