{"doi":"10.1093/function/zqae003","title":"Phosphodiesterases Mediate the Augmentation of Myogenic Constriction by Inhibitory G Protein Signaling and is Negatively Modulated by the Dual Action of RGS2 and 5","abstract":"Abstract G protein regulation by regulators of G protein signaling (RGS) proteins play a key role in vascular tone maintenance. The loss of Gi/o and Gq/11 regulation by RGS2 and RGS5 in non-pregnant mice is implicated in augmented vascular tone and decreased uterine blood flow (UBF). RGS2 and 5 are closely related and co-expressed in uterine arteries (UA). However, whether and how RGS2 and 5 coordinate their regulatory activities to finetune G protein signaling and regulate vascular tone are unclear. Here, we determined how the integrated activity of RGS2 and 5 modulates vascular tone to promote UBF. Using ultrasonography and pressure myography, we examined uterine hemodynamics and myogenic tone (MT) of UA of wild type (WT), Rgs2−/−, Rgs5−/−, and Rgs2/5 dbKO mice. We found that MT was reduced in Rgs5−/− relative to WT or Rgs2−/− UA. Activating Gi/o with dopamine increased, whereas exogenous cAMP decreased MT in Rgs5−/− UA to levels in WT UA. Dual deletion of Rgs2 and 5 abolished the reduced MT due to the absence of Rgs5 and enhanced dopamine-induced Gi/o effects in Rgs2/5 dbKO UA. Conversely, and as in WT UA, Gi/o inhibition with pertussis toxin or exogenous cAMP decreased MT in Rgs2/5 dbKO to levels in Rgs5−/− UA. Inhibition of phosphodiesterases (PDE) concentration-dependently decreased and normalized MT in all genotypes, and blocked dopamine-induced MT augmentation in Rgs2−/−, Rgs5−/−, and Rgs2/5 dbKO UA. We conclude that Gi/o augments UA MT in the absence of RGS2 by a novel mechanism involving PDE-mediated inhibition of cAMP-dependent vasodilatation..","journal":"Function","year":2024,"id":472968,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1074297,"name":"Nia Smith","orcid":null,"position":1,"is_corresponding":false},{"id":680641,"name":"Alethia J Dixon","orcid":"0000-0002-4374-0688","position":2,"is_corresponding":false},{"id":329350,"name":"Patrick Osei‐Owusu","orcid":"0000-0002-4581-7044","position":3,"is_corresponding":false},{"id":973955,"name":"Bo Sun","orcid":"0000-0002-0388-1451","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:06:01.000126Z","pmid":"38486977","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":[]}