{"doi":"10.3390/ijms24097887","title":"The Triad Na+ Activated Na+ Channel (Nax)—Salt Inducible KINASE (SIK) and (Na+ + K+)-ATPase: Targeting the Villains to Treat Salt Resistant and Sensitive Hypertension","abstract":"The Na+-activated Na+ channel (Nax) and salt-inducible kinase (SIK) are stimulated by increases in local Na+ concentration, affecting (Na+ + K+)-ATPase activity. To test the hypothesis that the triad Nax/SIK/(Na+ + K+)-ATPase contributes to kidney injury and salt-sensitive hypertension (HTN), uninephrectomized male Wistar rats (200 g; n = 20) were randomly divided into 4 groups based on a salt diet (normal salt diet; NSD—0.5% NaCl—or high-salt diet; HSD—4% NaCl) and subcutaneous administration of saline (0.9% NaCl) or deoxycorticosterone acetate (DOCA, 8 mg/kg), as follows: Control (CTRL), CTRL-Salt, DOCA, and DOCA-Salt, respectively. After 28 days, the following were measured: kidney function, blood pressure, (Na+ + K+)-ATPase and SIK1 kidney activities, and Nax and SIK1 renal expression levels. SIK isoforms in kidneys of CTRL rats were present in the glomerulus and tubular epithelia; they were not altered by HSD and/or HTN. CTRL-Salt rats remained normotensive but presented slight kidney function decay. HSD rats displayed augmentation of the Nax/SIK/(Na+ + K+)-ATPase pathway. HTN, kidney injury, and kidney function decay were present in all DOCA rats; these were aggravated by HSD. DOCA rats presented unaltered (Na+ + K+)-ATPase activity, diminished total SIK activity, and augmented SIK1 and Nax content in the kidney cortex. DOCA-Salt rats expressed SIK1 activity and downregulation in (Na+ + K+)-ATPase activity in the kidney cortex despite augmented Nax content. The data of this study indicate that the (Na+ + K+)-ATPase activity response to SIK is attenuated in rats under HSD, independent of HTN, as a mechanism contributing to kidney injury and salt-sensitive HTN.","journal":"International Journal of Molecular Sciences","year":2023,"id":371059,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9645,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1130710,"name":"Dayene S Gomes","orcid":"0000-0001-8488-6993","position":1,"is_corresponding":false},{"id":1130711,"name":"Alessandro M. Souza","orcid":"0000-0001-9241-8452","position":2,"is_corresponding":false},{"id":1130712,"name":"Fernanda M. Ferrão","orcid":"0000-0001-5163-321X","position":3,"is_corresponding":false},{"id":1130713,"name":"Zoe Vallotton","orcid":"0009-0000-9776-3298","position":4,"is_corresponding":false},{"id":388202,"name":"Venkateswara R. Gogulamudi","orcid":"0000-0002-8349-6640","position":5,"is_corresponding":false},{"id":1130714,"name":"Jennifer Lowe","orcid":"0000-0001-7378-4561","position":6,"is_corresponding":false},{"id":1130715,"name":"Dulce Elena Casarini","orcid":"0000-0003-1912-4292","position":7,"is_corresponding":false},{"id":388207,"name":"Minolfa C. Prieto","orcid":"0000-0002-0199-3193","position":8,"is_corresponding":false},{"id":388206,"name":"Lucienne S. Lara","orcid":"0000-0002-2204-8799","position":9,"is_corresponding":false},{"id":389421,"name":"Sabrina Ribeiro Gonsalez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:15:45.330525Z","pmid":"37175599","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}