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Enhanced and uneven hypoxic pulmonary vasoconstriction is an important pathogenic factor of hypoxic PE. We hypothesized that the potent vasodilator relaxin might reduce hypoxic pulmonary vasoconstriction and prevent PE formation. Furthermore, as relaxin has shown beneficial effects in acute heart failure, we expected that relaxin might also improve LV inotropic function in hypoxia. Forty-two rats were exposed over 24\u00a0h to normoxia or hypoxia (10% N<jats:sub>2<\/jats:sub>in O<jats:sub>2<\/jats:sub>). They were infused with either 0.9% NaCl solution (normoxic\/hypoxic controls) or relaxin at two doses (15 and 75\u00a0\u03bcg\u00a0kg<jats:sup>\u22121<\/jats:sup>\u00a0day<jats:sup>\u22121<\/jats:sup>). After 24\u00a0h, hemodynamic measurements and bronchoalveolar lavage were performed. Lung tissue was obtained for histological and immunohistochemical analyses. Hypoxic control rats presented significant depression of LV systolic pressure by 19% and of left and right ventricular contractility by about 40%. Relaxin did not prevent the hypoxic decrease in LV inotropic function, but re-increased right ventricular contractility. Moreover, hypoxia induced moderate interstitial PE and inflammation in the lung. Contrasting to our hypothesis, relaxin did not prevent hypoxia-induced pulmonary edema and inflammation. In hypoxic control rats, PE was similarly distributed in the apical and basal lung lobes. In relaxin-treated rats, PE index was 35\u201340% higher in the apical than in the basal lobe, which is probably due to gravity effects. We suggest that relaxin induced exaggerated vasodilation, and hence pulmonary overperfusion. In conclusion, the results show that relaxin does not prevent but rather may aggravate PE formation.<\/jats:p>","DOI":"10.1007\/s00424-022-02720-9","type":"journal-article","created":{"date-parts":[[2022,7,2]],"date-time":"2022-07-02T03:28:15Z","timestamp":1656732495000},"page":"1053-1067","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Relaxin does not prevent development of hypoxia-induced pulmonary edema in rats"],"prefix":"10.1007","volume":"474","author":[{"given":"Ute","family":"Kowalleck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed A. 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