{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:10:16Z","timestamp":1790359816532,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T00:00:00Z","timestamp":1545955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Adverse cardiovascular effects, including hypertension, were described in patients with different cancers treated with tyrosine kinase inhibitors (TKI). The mechanism of TKI-related hypertension is still debated. The aim of this work was to study the effects of TKI on blood pressure (BP), searching for a relationship with possible causative factors in patients with metastatic renal cell carcinoma. We included 29 patients in a prospective, observational study; 22 were treated with a first-line drug (sunitinib), while seven participated in the second-line treatment (axitinib or cabozantinib). Patients were investigated at the beginning of antiangiogenic therapy (T0) and at one (T1), three (T2), and six months (T3) after treatment. Patients were evaluated by office blood pressure (BP) and ultrasonography to measure flow-mediated dilatation (FMD), and carotid artery distensibility (cDC) by echocardiography and nailfold capillaroscopy. Plasma endothelin-1 (p-ET-1), urine nitrates, and proteins were also measured. At T1, systolic BP, along with U proteins and p-ET-1, increased significantly. In patients with a clinically significant increase in BP (defined as either the need for an antihypertensive drug or systolic blood pressure (SBP) T1\u2013T0 \u226510 and\/or SBP \u2265140 mmHg and\/or diastolic blood pressure (DBP) T1\u2013T0 \u22655 and\/or DBP \u226590 mmHg), the urine nitrate concentration was lower at T0, whereas there were no differences in the p-ET-1 and U proteins. Seventeen participants showed changes in the capillaroscopic pattern at T1 with no association with BP increases. There were no differences in the FMD, cDC, and echocardiographic parameters. Our findings are consistent with those of previous studies about BP increases by TKI, and suggest a role of nitric oxide in BP maintenance in this population.<\/jats:p>","DOI":"10.3390\/cancers11010030","type":"journal-article","created":{"date-parts":[[2018,12,28]],"date-time":"2018-12-28T11:52:42Z","timestamp":1545997962000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Effects of Antiangiogenetic Drugs on Microcirculation and Macrocirculation in Patients with Advanced-Stage Renal Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0402-4176","authenticated-orcid":false,"given":"Andrea","family":"Dalbeni","sequence":"first","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-4339","authenticated-orcid":false,"given":"Chiara","family":"Ciccarese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Oncology Unit, University of Verona, 37126 Verona, Italy"},{"name":"Department of Medicine, Oncology Unit, Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Bevilacqua","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Benati","sequence":"additional","affiliation":[{"name":"Department of neurosciences, biomedicine and movement sciences, Section of Clinical Biochemistry, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Caimmi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cerrito","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Fam\u00e0","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Iacovelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Oncology Unit, University of Verona, 37126 Verona, Italy"},{"name":"Department of Medicine, Oncology Unit, Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4269-9924","authenticated-orcid":false,"given":"Francesco","family":"Meneguzzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Oncology Unit, University of Verona, 37126 Verona, Italy"},{"name":"Department of Medicine, Section of Internal Medicine, University Laboratory for Medical Research (LURM) and Regional Centre for the Study of Platelets, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Minuz","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Montagnana","sequence":"additional","affiliation":[{"name":"Department of neurosciences, biomedicine and movement sciences, Section of Clinical Biochemistry, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Orsolini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9692-2293","authenticated-orcid":false,"given":"Maurizio","family":"Rossini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1378-4962","authenticated-orcid":false,"given":"Gianpaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Department of Medicine, Oncology Unit, University of Verona, 37126 Verona, Italy"},{"name":"Department of Medicine, Oncology Unit, Fondazione Policlinico Universitario \u201cAgostino Gemelli\u201d IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ombretta","family":"Viapiana","sequence":"additional","affiliation":[{"name":"Department of Medicine, Rheumatology Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8910-7378","authenticated-orcid":false,"given":"Cristiano","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of Medicine, General Medicine and Hypertension Unit, University of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1124\/jpet.105.084145","article-title":"Role of Tyrosine Kinase Inhibitors in Cancer Therapy","volume":"315","author":"Arora","year":"2005","journal-title":"J. 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