Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice.
Vascular nitric oxide and superoxide anion contribute to sex-specific programmed cardiovascular physiology in mice.
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血管一氧化氮和超氧阴离子有助于小鼠性别特异性的程序性心血管生理学。
DOI：
10.1152/ajpregu.90756.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Lamb,FredS
中科院分区：
文献类型：
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作者：
Roghair,RobertD;Segar,JeffreyL;Volk,KennethA;Chapleau,MarkW;Dallas,LindsayM;Sorenson,AnnaR;Scholz,ThomasD;Lamb,FredS
宫内环境紊乱与成人高血压的发生有关。我们试图评估性别、一氧化氮和活性氧（ROS）在程序性心血管疾病中的相互作用。通过母体饮食干预（DI;用碳水化合物和脂肪部分取代蛋白质）或甘珀酸给药（CX，以增加胎儿糖皮质激素暴露）诱导小鼠编程。在基线、高盐一周后和高盐加一氧化氮合酶抑制剂（byl-NAME）一周后，通过无线电遥测记录成人血压和自发活动。在雄性后代中，DI或CX编程血压升高，Nω-硝基-L-精氨酸甲酯给药会加重血压升高，但单独高盐不会。DI雄性后代的肠系膜阻力血管对ACh和硝普钠的舒张功能受损，可被过氧化氢酶和超氧化物歧化酶阻断。CX暴露的雌性动物血压正常，而DI雌性动物出现一氧化氮合酶依赖性低血压和增强的肠系膜扩张。尽管不同的心血管表型，男性和女性的DI后代显示增加的自发活动和主动脉超氧化物的生产。尽管血压不同，DI和CX暴露的女性心脏压力反射敏感性降低。总之，母亲营养不良和胎儿糖皮质激素暴露程序增加男性，但不是女性后代的动脉压。虽然母体DI增加了超氧化物介导的血管收缩和一氧化氮介导的血管舒张，但这些因素的平衡有利于男性高血压和女性低血压的发展。
Intrauterine environmental pertubations have been linked to the development of adult hypertension. We sought to evaluate the interrelated roles of sex, nitric oxide, and reactive oxygen species (ROS) in programmed cardiovascular disease. Programming was induced in mice by maternal dietary intervention (DI; partial substitution of protein with carbohydrates and fat) or carbenoxolone administration (CX, to increase fetal glucocorticoid exposure). Adult blood pressure and locomotor activity were recorded by radiotelemetry at baseline, after a week of high salt, and after a week of high salt plus nitric oxide synthase inhibition (byl-NAME). In male offspring, DI or CX programmed an elevation in blood pressure that was exacerbated by Nω-nitro-l-arginine methyl ester administration, but not high salt alone. Mesenteric resistance vessels from DI male offspring displayed impaired vasorelaxation to ACh and nitroprusside, which was blocked by catalase and superoxide dismutase. CX-exposed females were normotensive, while DI females had nitric oxide synthase-dependent hypotension and enhanced mesenteric dilation. Despite the disparate cardiovascular phenotypes, both male and female DI offspring displayed increases in locomotor activity and aortic superoxide production. Despite dissimilar blood pressures, DI and CX-exposed females had reductions in cardiac baroreflex sensitivity. In conclusion, both maternal malnutrition and fetal glucocorticoid exposure program increases in arterial pressure in male but not female offspring. While maternal DI increased both superoxide-mediated vasoconstriction and nitric oxide mediated vasodilation, the balance of these factors favored the development of hypertension in males and hypotension in females.