{"title":"Inhibition of CB1R in the Hypothalamic Paraventricular Nucleus Ameliorates Hypertension Through Wnt/β-Catenin/RAS Pathway.","authors":"Hong-Li Gao, Yu Yang, Hua Tian, Li-Yan Fu, Kai-Li Liu, Xiu-Yue Jia, Xiao-Lian Shi, Yu-Ming Kang, Xiao-Jing Yu","doi":"10.1007/s12012-024-09938-2","DOIUrl":null,"url":null,"abstract":"<p><p>The hypothalamic paraventricular nucleus (PVN), as an important integrating center, plays a prominent role in the pathogenesis of hypertension, in maintaining the stability of cardiovascular activity through peripheral sympathetic nervous activity and secretion of various humoral factors. Acknowledging that the mechanistic targets of the endocannabinoid type 1 receptor (CB1R) are the key signaling systems involved in the regulation of hypertension, we sought to clarify whether inhibition of CB1R within the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats were randomly assigned to different groups and treated with bilateral PVN injections of AM251 (CB1R antagonist, 10 µg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for four weeks. Bilateral PVN injections of AM251 significantly decreased the heart rate, the body weight and the mean arterial pressure in SHRs. AM251 lowered the expression of CB1R, Wnt3, active-β-catenin, p-IKKβ, RAS components, pro-inflammatory cytokines and elevated the expression level of Glycogen synthase kinase3β and Superoxide Dismutase in the PVN of hypertensive rats. Our findings suggest that inhibition of CB1R in the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway and broaden our current understanding of the pathological mechanism and clinical treatment of hypertension.</p>","PeriodicalId":9570,"journal":{"name":"Cardiovascular Toxicology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12012-024-09938-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
Abstract
The hypothalamic paraventricular nucleus (PVN), as an important integrating center, plays a prominent role in the pathogenesis of hypertension, in maintaining the stability of cardiovascular activity through peripheral sympathetic nervous activity and secretion of various humoral factors. Acknowledging that the mechanistic targets of the endocannabinoid type 1 receptor (CB1R) are the key signaling systems involved in the regulation of hypertension, we sought to clarify whether inhibition of CB1R within the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway. Spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats were randomly assigned to different groups and treated with bilateral PVN injections of AM251 (CB1R antagonist, 10 µg/h) or vehicle (artificial cerebrospinal fluid, aCSF) for four weeks. Bilateral PVN injections of AM251 significantly decreased the heart rate, the body weight and the mean arterial pressure in SHRs. AM251 lowered the expression of CB1R, Wnt3, active-β-catenin, p-IKKβ, RAS components, pro-inflammatory cytokines and elevated the expression level of Glycogen synthase kinase3β and Superoxide Dismutase in the PVN of hypertensive rats. Our findings suggest that inhibition of CB1R in the PVN ameliorates hypertension through Wnt/β-catenin/RAS pathway and broaden our current understanding of the pathological mechanism and clinical treatment of hypertension.
期刊介绍:
Cardiovascular Toxicology is the only journal dedicated to publishing contemporary issues, timely reviews, and experimental and clinical data on toxicological aspects of cardiovascular disease. CT publishes papers that will elucidate the effects, molecular mechanisms, and signaling pathways of environmental toxicants on the cardiovascular system. Also covered are the detrimental effects of new cardiovascular drugs, and cardiovascular effects of non-cardiovascular drugs, anti-cancer chemotherapy, and gene therapy. In addition, Cardiovascular Toxicology reports safety and toxicological data on new cardiovascular and non-cardiovascular drugs.