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Sex is a vital factor to consider when assessing drug response in pre\u2010clinical and clinical studies. In this study, the diuretic effect of the KOP agonist, U50488 (1\u201310\u2009mg\/kg), was investigated in both adult female and male Wistar rats that were either normally hydrated or water\u2010loaded. The KOP antagonist norbinaltorphimine (norBNI, 10\u2009mg\/kg) was administered 24\u2009h prior to U50488 to confirm the involvement of KOP. U50488 elicited a significant diuretic response at doses \u2265 3\u2009mg\/kg in both female and male rats independent of hydration status. U50488 diuretic effects were inhibited by norBNI pre\u2010administration. Water\u2010loading reduced data variability for urine volume in males, but not in females, compared with normally hydrated rats. Sex differences were also evident in U50488 eliciting a significant increase in sodium and potassium ion excretion only in males. This may suggest different mechanisms of U50488 diuretic action in males where renal excretion mechanisms are directly affected more than in females.<\/jats:p>","DOI":"10.1111\/bcpt.14008","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T03:30:15Z","timestamp":1712547015000},"page":"792-804","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effects of sex and hydration status on kappa opioid receptor\u2010mediated diuresis in rats"],"prefix":"10.1111","volume":"134","author":[{"given":"Hasnain M.","family":"Lalji","sequence":"first","affiliation":[{"name":"Department of Life Sciences University of Bath  Bath UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Life Sciences University of Bath  Bath 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