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This phase I, open\u2010label, pharmacodynamic study investigated vascular effects of buloxibutid in five healthy male volunteers. Subjects were administered intra\u2010arterial infusions of buloxibutid for 5\u2009min in ascending doses of 3, 10, 30, 100, and 200\u2009\u03bcg\/min, infused sequentially in the forearm. Infusions of sodium nitroprusside (SNP) solution in doses of 0.8\u20133.2\u2009\u03bcg\/min were administered as a positive control. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Safety and tolerability of intra\u2010arterial administrations of buloxibutid were evaluated. Following infusion of buloxibutid in doses of 3\u2013200\u2009\u03bcg\/min, the range of increase in FBF was 27.8%, 17.2%, 37.0%, 28.5%, and 60.5%, compared to the respective baseline. The largest increase was observed in the highest dose group. Infusions of SNP as a positive control, increased FBF 230\u2013320% compared to baseline. Three adverse events (AEs) of mild intensity, not related to buloxibutid or SNP, were reported for two subjects. Two of these AEs were related to study procedures. There were no clinically relevant changes in arterial blood pressure during the study period. Intra\u2010arterial infusion of buloxibutid in low, ascending doses increased FBF, indicating that buloxibutid may be effective in conditions associated with endothelial dysfunction. Venous occlusion plethysmography was found to be a useful method to explore pharmacodynamic vascular effects of novel AT2R agonists, while avoiding systemic adverse effects.<\/jats:p>","DOI":"10.1111\/cts.13735","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T10:05:57Z","timestamp":1707732357000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Utilizing venous occlusion plethysmography to assess vascular effects: A study with buloxibutid, an angiotensin <scp>II<\/scp> type 2 receptor agonist"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9462-1785","authenticated-orcid":false,"given":"Erik","family":"Rein\u2010Hedin","sequence":"first","affiliation":[{"name":"CTC Clinical Trial Consultants AB  Uppsala Sweden"},{"name":"Department of Surgical Sciences, Plastic Surgery Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5903-2918","authenticated-orcid":false,"given":"Folke","family":"Sj\u00f6berg","sequence":"additional","affiliation":[{"name":"CTC Clinical Trial Consultants AB  Uppsala Sweden"},{"name":"Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Ganslandt","sequence":"additional","affiliation":[{"name":"Vicore Pharma AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-8392","authenticated-orcid":false,"given":"Johan","family":"Skoog","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology and Department of Health, Medicine and Caring Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6536-468X","authenticated-orcid":false,"given":"Helene","family":"Zachrisson","sequence":"additional","affiliation":[{"name":"Department of Clinical Physiology and Department of Health, Medicine and Caring Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Bengtsson","sequence":"additional","affiliation":[{"name":"StatMind AB  Lund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl\u2010Johan","family":"Dalsgaard","sequence":"additional","affiliation":[{"name":"Vicore Pharma AB  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000281"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e328349ae0d"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2015.01.004"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.34.5.1112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.congress-2022.4402"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac426"},{"key":"e_1_2_12_8_1","unstructured":"International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use.Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. 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