{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:53:13Z","timestamp":1792896793920,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T00:00:00Z","timestamp":1687824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Ateneo Ricerca"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels.<\/jats:p>","DOI":"10.3390\/ijms241310710","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"10710","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation"],"prefix":"10.3390","volume":"24","author":[{"given":"Giovanna","family":"Castoldi","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Carletti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Traslazionale e di Precisione, Sapienza Universit\u00e0 di Roma, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ippolito","sequence":"additional","affiliation":[{"name":"Laboratorio Analisi Chimico Cliniche, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Colzani","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-9641","authenticated-orcid":false,"given":"Sara","family":"Pelucchi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6181-089X","authenticated-orcid":false,"given":"Gianpaolo","family":"Zerbini","sequence":"additional","affiliation":[{"name":"Unita\u2019 Complicanze del Diabete, IRCCS Istituto Scientifico San Raffaele, 20132 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3024-0457","authenticated-orcid":false,"given":"Gianluca","family":"Perseghin","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Milano-Bicocca, 20900 Monza, Italy"},{"name":"Dipartimento di Medicina Interna e Riabilitazione, Policlinico di Monza, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Zatti","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Universit\u00e0 degli Studi di Milano-Bicocca, 20900 Monza, Italy"},{"name":"Clinica Ortopedica, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4696-0560","authenticated-orcid":false,"given":"Cira R. T.","family":"di Gioia","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Radiologiche, Oncologiche e Anatomopatologiche, Istituto di Anatomia Patologica, Sapienza Universit\u00e0 di Roma, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes","volume":"373","author":"Zinman","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1056\/NEJMoa1515920","article-title":"Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes","volume":"375","author":"Wanner","year":"2016","journal-title":"N. Engl. J. 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