{"doi":"10.7554/elife.56655","title":"Intravascular flow stimulates PKD2 (polycystin-2) channels in endothelial cells to reduce blood pressure","abstract":"PKD2 (polycystin-2, TRPP1), a TRP polycystin channel, is expressed in endothelial cells (ECs), but its physiological functions in this cell type are unclear. Here, we generated inducible, EC-specific Pkd2 knockout mice to examine vascular functions of PKD2. Data show that a broad range of intravascular flow rates stimulate EC PKD2 channels, producing vasodilation. Flow-mediated PKD2 channel activation leads to calcium influx that activates SK/IK channels and eNOS serine 1176 phosphorylation in ECs. These signaling mechanisms produce arterial hyperpolarization and vasodilation. In contrast, EC PKD2 channels do not contribute to acetylcholine-induced vasodilation, suggesting stimulus-specific function. EC-specific PKD2 knockout elevated blood pressure in mice without altering cardiac function or kidney anatomy. These data demonstrate that flow stimulates PKD2 channels in ECs, leading to SK/IK channel and eNOS activation, hyperpolarization, vasodilation and a reduction in systemic blood pressure. Thus, PKD2 channels are a major component of functional flow sensing in the vasculature.","journal":"eLife","year":2020,"id":66602,"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":50,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":353061,"name":"M. Dennis Leo","orcid":"0000-0002-2703-4011","position":1,"is_corresponding":false},{"id":353062,"name":"Carlos Fernández‐Peña","orcid":"0000-0002-0726-3204","position":2,"is_corresponding":false},{"id":353063,"name":"Raquibul Hasan","orcid":"0000-0002-6897-2901","position":3,"is_corresponding":false},{"id":353064,"name":"Wen Yin","orcid":"0000-0003-4418-9231","position":4,"is_corresponding":false},{"id":353065,"name":"Alejandro Mata‐Daboin","orcid":"0000-0003-1831-7842","position":5,"is_corresponding":false},{"id":353066,"name":"Simon Bulley","orcid":"0000-0001-5985-0489","position":6,"is_corresponding":false},{"id":353067,"name":"Jesse Gammons","orcid":"0000-0003-1916-8375","position":7,"is_corresponding":false},{"id":353068,"name":"Salvatore Mancarella","orcid":"0000-0001-9049-4697","position":8,"is_corresponding":false},{"id":353069,"name":"Jonathan H. Jaggar","orcid":"0000-0003-1505-3335","position":9,"is_corresponding":false},{"id":353060,"name":"Charles Mackay","orcid":"0000-0002-2875-0677","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-18T21:14:50.590588Z","pmid":"32364494","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":[]}