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These may include peripheral and central nervous system abnormalities. However, accumulating evidence from animals with experimental models of congestive heart failure and renal dysfunction as well as humans with the cardiorenal syndrome suggests that alterations in neural pathways, from and to the kidneys and the heart, including the central nervous system are involved in regulating sympathetic outflow and may be critically important in the alterations in neurohumoral drive, autonomic reflexes, and fluid balance commonly observed in the cardiorenal syndrome. This review focuses on studies implicating neural pathways, particularly the afferent and efferent signals from the heart and the kidneys integrating at the level of the paraventricular nucleus in the hypothalamus to alter neurohumoral drive, autonomic pathways, and fluid balance. Further, it explores the potential mechanisms of action for the known beneficial use of various medications or potential novel therapeutic manipulations for the treatment of the cardiorenal syndrome. A comprehensive understanding of these mechanisms will enhance our ability to treat cardiorenal conditions and their cardiovascular complications more efficaciously and thoroughly.<\/jats:p>","DOI":"10.1161\/circresaha.122.319989","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T14:00:21Z","timestamp":1652364021000},"page":"1601-1617","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":88,"title":["Cardiorenal Syndrome: The Role of Neural Connections Between the Heart and the Kidneys"],"prefix":"10.1161","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4500-0819","authenticated-orcid":true,"given":"Kaushik P.","family":"Patel","sequence":"first","affiliation":[{"name":"Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha (K.P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0567-1458","authenticated-orcid":true,"given":"Kenichi","family":"Katsurada","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Department of Internal Medicine (K.K.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan."},{"name":"Division of Clinical Pharmacology, Department of Pharmacology (K.K.), Jichi Medical University School of Medicine, Shimotsuke, Tochigi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1660-3573","authenticated-orcid":true,"given":"Hong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion (H.Z.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0803"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq066"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-020-00842-w"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2011.11.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2010.03.019"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2011.11.004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3282f357da"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1996.463796000.x"},{"key":"e_1_3_3_10_2","first-page":"325","article-title":"Pathophysiology of edema in congestive heart failure.","volume":"2","author":"Navas JP","year":"1993","unstructured":"Navas, JP, Martinez-Maldonado, M. 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