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Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol\u2010naive females to produce alcohol\u2010 and control\u2010sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch\u2010clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)\u2010mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII\u2010induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L\u2010type voltage\u2010dependent calcium channel (L\u2010Ca<jats:sup>2+<\/jats:sup>) current at baseline and after AngII\u2010stimulation was higher in VSMCs. Influence of large\u2010conductance calcium\u2010activated potassium channel (BK<jats:sub>C<\/jats:sub><jats:sub>a<\/jats:sub>) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII\u2010mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII\u2010mediated vasoconstriction in offspring MCA via ROS\u2010AT1R. Alcohol consumption increased intracellular calcium via L\u2010Ca<jats:sup>2+<\/jats:sup> channel and endoplasmic reticulum and decreased BK<jats:sub>Ca<\/jats:sub> function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/adb.13385","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T06:24:35Z","timestamp":1710570275000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Paternal preconception alcohol consumption increased Angiotensin II\u2010mediated vasoconstriction in male offspring cerebral arteries via oxidative stress\u2010AT1R pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Ze","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute for Fetology First Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Fetology First Hospital of Soochow University  Suzhou 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