{"doi":"10.1111/jch.14152","title":"Thyroid hormones regulate both cardiovascular and renal mechanisms underlying hypertension","abstract":"Physiologically, thyroid hormones are able to affect the fundamental determinants of blood pressure (BP): cardiac output, peripheral vascular resistance, and kidney function (Figure 1). The thyroid-mediated fine orchestration of cardiac contractility, vascular tone, and renal homeostasis confers to the thyroid gland a key role in the pathophysiology of hypertension. Indeed, BP is altered across the entire spectrum of thyroid diseases.1 However, the effects of thyroid disorders on BP are very intricate, mirroring the multifactorial and disparate actions of thyroid hormones on cardiovascular system and metabolism. In fact, if on one hand thyroid hormones increase contractility, tachycardia, and basal metabolic rate, which are positive regulators of BP, on the other hand they are able to decrease systemic vascular resistance, thereby lowering BP. Ergo, the balance between these opposite actions is eventually able to achieve an optimal regulation of BP, and modifications in thyroid hormones availability, both hypo- and hyperthyroidism, can alter this fine equilibrium. A wide and consistent literature is available on the association between thyroid disorders and hypertension.2 However, only few studies have explored the relationship between BP and thyroid hormones in healthy subjects, in order to understand whether different levels of thyroid hormones, within a physiological range, can reflect changes in BP. In this context, in the current issue of the Journal, Jamal and colleagues offer their elegant investigation conducted on 691 healthy subjects.3 The authors elegantly show that in a physiological context, augmented serum levels of triiodothyronine (T3) and thyroxine (T4) are associated with an increase of both peripheral and central BP. A strength of the study is denoted by the choice to measure central BP, which is suggested to be a more reliable prognostic marker in cardiovascular disorder compared to conventional brachial cuff BP.4 The authors open the scenario for a potential role of serum level of thyroid hormones as predictor of central BP, and therefore a powerful prognostic factor of hypertension and cardiovascular complications. Of course, further studies are needed to verify and better understand the proposed relationship, even to enlarge the sample population. Moreover, in future studies it could be interesting to perform a time-course assessment of thyroid hormones levels (which usually oscillate in the same subject) evaluating their effects on BP variation. Indeed, a circadian rhythm has been demonstrated for triiodothyronine (T3), with a periodicity that lags behind thyroid-stimulating hormone (TSH).5, 6 Another aspect that needs to be further examined is the potential role of the effects of T3 and T4 on the intricate interaction between cardiovascular and renal systems.7-9 To better characterize the complex context in which the study performed by Jamal and colleagues3 fits, here we propose a summary of the central mechanisms by which thyroid hormones can affect cardiac output, vascular resistances, and kidney function. We also summarize the results of the most recent clinical studies focused on the relationship between thyroid hormones and hypertension. Among the numerous transporters responsible for the intracellular uptake of T3 and T4, three proteins were found to be expressed in the heart so far.10, 11 Two of them—monocarboxylate transporter 8 (MCT8) and large neutral amino acids transporter small subunit 2 (LAT2)—transport across the plasma membrane both T3 and thyroxine, whereas MCT10 is more effective in T3 transport.12 Cardiomyocytes express also enzymes regulating thyroid hormones metabolism—type I and II iodothyronine deiodinases (DIO1, DIO2) and T4 5-deiodinase (DIO3).13, 14 DIO1 and DIO2 convert biologically inactive T4 into active T3; DIO3 catabolizes both hormones, thus ceasing their biological activity. Interestingly, local upregulation of DIO3 expression can produce a tissue-specific decrease in T","journal":"Journal of Clinical Hypertension","year":2020,"id":99638,"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":30,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9446,"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":225558,"name":"Marco Bruno Morelli","orcid":"0000-0001-5540-0368","position":1,"is_corresponding":false},{"id":225557,"name":"Jessica Gambardella","orcid":"0000-0001-5563-3153","position":2,"is_corresponding":false},{"id":334315,"name":"Angela Lombardi","orcid":"0000-0001-5421-9970","position":3,"is_corresponding":false},{"id":225561,"name":"Gaetano Santulli","orcid":"0000-0001-7231-375X","position":4,"is_corresponding":false},{"id":490256,"name":"Stanislovas S. Jankauskas","orcid":"0000-0002-0843-5098","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-18T22:38:09.754371Z","pmid":"33377271","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":[]}