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

IF 3.1 3区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Addiction Biology Pub Date : 2024-03-15 DOI:10.1111/adb.13385

Ze Zhang, Yumeng Zhang, Mingxing Liu, Hongyu Su, Yun He, Qiutong Zheng, Zhice Xu, Jiaqi Tang

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Abstract

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 (BK_C_a) 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 BK_Ca function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

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父亲孕前饮酒会通过氧化应激-AT1R途径增加血管紧张素II介导的男性后代脑动脉血管收缩。

饮酒风靡全球，并与心血管疾病密切相关。父亲在怀孕前饮酒对后代脑动脉的影响尚不清楚。雄性大鼠在与不饮酒的雌性大鼠交配前，会被随机给予酒精或水，以产生饮酒后代和对照组后代。使用丹麦 Myo Technology 公司的金属丝肌电图仪、膜片钳、IONOPTIX、免疫荧光和定量 PCR 对大脑中动脉（MCA）进行了检测。饮酒主要通过 AT1R 增强血管紧张素 II（AngII）介导的雄性后代 MCA 收缩。PD123,319仅能增强血管紧张素II诱导的对照组后代收缩。AngII和Bay K8644诱导酒精后代MCA血管平滑肌细胞（VSMC）产生更强的细胞内钙瞬态。在基线和 AngII 刺激后，血管平滑肌细胞中的 L 型电压依赖性钙通道（L-Ca2+）电流较高。大电导钙激活钾通道（BKC a）的影响较低。咖啡因在酒精后代中诱导更强的收缩和细胞内钙释放。酒精性 MCA 中的超氧阴离子高于对照组。Tempol和三氟丙酮可减轻AngⅡ介导的收缩，而酒精组的抑制作用明显高于对照组。酒精 MCA 中线粒体肿胀。尽管酒精组的 Kcnma1 和 Prkce 表达较低，但许多基因的表达却较高。缺氧诱导了活性氧的产生，并增加了对照组 MCA 和大鼠主动脉平滑肌细胞系中 AT1R 的表达。总之，本研究首次证明父亲孕前饮酒可通过ROS-AT1R增强AngII介导的子代MCA血管收缩。饮酒会通过 L-Ca2+ 通道和内质网增加细胞内钙，并降低 BKCa 的功能。本研究为男性生殖健康和脑血管疾病的发育起源提供了新的信息。

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来源期刊

Addiction Biology 生物-生化与分子生物学

CiteScore

8.10

自引率

2.90%

发文量

118

审稿时长

6-12 weeks

期刊介绍： Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.