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This study was designed to characterize the functional cardiovascular pharmacology of SER100<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>, including experimental models of cardiovascular disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Haemodynamic, ECG parameters and heart rate variability (HRV) were determined using radiotelemetry in healthy, conscious mice. The haemodynamic and vascular effects of SER100 were also evaluated in two models of cardiovascular disease, spontaneously hypertensive rats (SHR) and murine hypoxia\u2010induced pulmonary hypertension (PH). To elucidate mechanisms underlying the pharmacology of SER100, acute blood pressure recordings were performed in anaesthetized mice, and the reactivity of rodent aorta and mesenteric arteries in response to electrical\u2010 and agonist\u2010stimulation assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>SER100 caused NOP receptor\u2010dependent reductions in mean arterial blood pressure and heart rate that were independent of NO. The hypotensive and vasorelaxant actions of SER100 were potentiated in SHR compared with Wistar Kyoto. Moreover, SER100 reduced several indices of disease severity in experimental PH. Analysis of HRV indicated that SER100 decreased the low\/high frequency ratio, an indicator of sympatho\u2010vagal balance, and in electrically stimulated mouse mesenteric arteries SER100 inhibited sympathetic\u2010induced contractions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>SER100 exerts a chronic hypotensive and bradycardic effects in rodents, including models of systemic and pulmonary hypertension. SER100 produces its cardiovascular effects, at least in part, by inhibition of cardiac and vascular sympathetic activity. SER100 may represent a novel therapeutic candidate in systemic and pulmonary hypertension.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13634","type":"journal-article","created":{"date-parts":[[2016,9,26]],"date-time":"2016-09-26T01:36:56Z","timestamp":1474853816000},"page":"3386-3401","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Functional pharmacological characterization of SER100 in cardiovascular health and disease"],"prefix":"10.1111","volume":"173","author":[{"given":"Inmaculada C","family":"Villar","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen J","family":"Bubb","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary 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