Paternal preconception alcohol consumption increased Angiotensin II‐mediated vasoconstriction in male offspring cerebral arteries via oxidative stress‐AT1R pathway

• Published in: Addiction biology Vol. 29; no. 3; pp. e13385 - n/a
• Main Authors: Zhang, Ze, Zhang, Yumeng, Liu, Mingxing, Su, Hongyu, He, Yun, Zheng, Qiutong, Xu, Zhice, Tang, Jiaqi
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2024; Wiley-Blackwell; John Wiley and Sons Inc
• Subjects: Alcohol; Alcohol Drinking; Alcohol use; Angiotensin; Angiotensin II; Angiotensin II - metabolism; Angiotensin II - pharmacology; Animals; Aorta; Caffeine; Calcium (intracellular); Calcium (reticular); Calcium - metabolism; Calcium channels (voltage-gated); Calcium conductance; Cardiovascular diseases; cerebral arteries; Cerebral Arteries - metabolism; Cerebrovascular diseases; Endoplasmic reticulum; Female; Hypoxia; Immunofluorescence; Intracellular; intracellular calcium; ion channel; Male; mitochondria; Offspring; Original; Oxidative Stress; paternal preconception alcohol consumption; Potassium conductance; Rats; Reactive oxygen species; Reproductive health; Smooth muscle; Superoxide anions; Tempol; Vascular diseases; Vasoconstriction; China; cerebral arteries; ion channel; angiotensin II; mitochondria; intracellular calcium; oxidative stress; paternal preconception alcohol consumption
• ISSN: 1355-6215; 1369-1600; 1369-1600
• DOI: 10.1111/adb.13385

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. 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‐naive females to produce alcohol‐ and control‐sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch‐clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)‐mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII‐induced 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‐type voltage‐dependent calcium channel (L‐Ca2+) current at baseline and after AngII‐stimulation was higher in VSMCs. Influence of large‐conductance calcium‐activated potassium channel (BKCa) 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‐mediated 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‐mediated vasoconstriction in offspring MCA via ROS‐AT1R. Alcohol consumption increased intracellular calcium via L‐Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases. Paternal preconception alcohol consumption increased angiotensin II (Ang II)‐mediated middle cerebral artery constriction in male offspring via oxidative stress‐AT1R pathway. Paternal preconception alcohol consumption increased the function of L‐type calcium channel and the content of endoplasmic reticulum calcium and decreased the function of large‐conductance calcium‐activated potassium channel (BKCa), which resulted in the increased constriction in the cerebral artery from alcohol offspring. Paternal preconception alcohol consumption affected growth and metabolism in offspring.