| http://purl.uniprot.org/citations/30925093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30925093 | http://www.w3.org/2000/01/rdf-schema#comment | "Activation of the brain renin-angiotensin system (RAS) is a pivotal step in the pathogenesis of hypertension. The paraventricular nucleus (PVN) of the hypothalamus is a critical part of the angiotensinergic sympatho-excitatory neuronal network involved in neural control of blood pressure and hypertension. However, the importance of the PVN (pro)renin receptor (PVN-PRR)-a key component of the brain RAS-in hypertension development has not been examined. In this study, we investigated the involvement and mechanisms of the PVN-PRR in DOCA-salt-induced hypertension, a mouse model of hypertension. Using nanoinjection of adeno-associated virus-mediated Cre recombinase expression to knock down the PRR specifically in the PVN, we report here that PVN-PRR knockdown attenuated the enhanced blood pressure and sympathetic tone associated with hypertension. Mechanistically, we found that PVN-PRR knockdown was associated with reduced activation of ERK (extracellular signal-regulated kinase)-1/2 in the PVN and rostral ventrolateral medulla during hypertension. In addition, using the genetically encoded Ca2+ biosensor GCaMP6 to monitor Ca2+-signaling events in the neurons of PVN brain slices, we identified a reduction in angiotensin II type 1 receptor-mediated Ca2+ activity as part of the mechanism by which PVN-PRR knockdown attenuates hypertension. Our study demonstrates an essential role of the PRR in PVN neurons in hypertension through regulation of ERK1/2 activation and angiotensin II type 1 receptor-mediated Ca2+ activity. NEW & NOTEWORTHY PRR knockdown in PVN neurons attenuates the development of DOCA-salt hypertension and autonomic dysfunction through a decrease in ERK1/2 activation in the PVN and RVLM during hypertension. In addition, PRR knockdown reduced AT1aR expression and AT1R-mediated calcium activity during hypertension. Furthermore, we characterized the neuronal targeting specificity of AAV serotype 2 in the mouse PVN and validated the advantages of the genetically encoded calcium biosensor GCaMP6 in visualizing neuronal calcium activity in the PVN."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpheart.00780.2018"xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Feng Y."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Li W."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Yamasaki E."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Watkins T."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Drumm B.T."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Cooper S.G."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Worker C.J."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Trebak F."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Gayban A.J.B."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/author | "Souza L.A.C."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/name | "Am J Physiol Heart Circ Physiol"xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/pages | "H1389-H1405"xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/title | "(Pro)renin receptor knockdown in the paraventricular nucleus of the hypothalamus attenuates hypertension development and AT1 receptor-mediated calcium events."xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://purl.uniprot.org/core/volume | "316"xsd:string |
| http://purl.uniprot.org/citations/30925093 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/30925093 |
| http://purl.uniprot.org/citations/30925093 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/30925093 |
| http://purl.uniprot.org/uniprot/#_Q1XID4-mappedCitation-30925093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30925093 |
| http://purl.uniprot.org/uniprot/#_Q9CYN9-mappedCitation-30925093 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/30925093 |
| http://purl.uniprot.org/uniprot/Q1XID4 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/30925093 |
| http://purl.uniprot.org/uniprot/Q9CYN9 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/30925093 |