N-Acetylcysteine Prevents Programmed Hypertension in Male Rat Offspring Born to Suramin-Treated Mothers

Tain You-Lin; Hsu Chien-Ning; Lee Chien-TeLin Yu-JuTsai Ching-Chou

摘要

Adulthood hypertension can be programmed by preeclampsia. Preeclampsia is associated with an imbalance in vasoactive factors, including nitric oxide (NO), hydrogen sulfide (H2S), and renin-angiotensin system (RAS). We examined whether maternal N-acetylcysteine (NAC) therapy prevented maternal suramin treatment-induced programmed hypertension in offspring and explored the effects of this therapy on NO, H2S, and RAS pathways in the kidneys. Pregnant Sprague-Dawley rats were intraperitoneally administered 60 mg/kg suramin alone on Gestational Days 10 and 11 and were treated with or without 1% NAC through drinking water during the entire pregnancy and lactation period. Male offspring were divided into four groups (n = 8-10/group): control, suramin, NAC, and suramin plus NAC. All rat offspring were euthanized at 12 wk of age. Maternal suramin treatment induced programmed hypertension in male offspring, which was prevented by maternal NAC therapy. Suramin-induced programmed hypertension was associated with increased plasma asymmetric dimethylarginine (ADMA, an NO synthase inhibitor) level, decreased plasma L-arginine-to-ADMA ratio, and decreased renal dimethylarginine dimethylaminohydrolase (an ADMA-metabolizing enzyme) activity. Protective effects of NAC against suramin-induced programmed hypertension were associated with an increase in plasma glutathione level, increase in renal 3-mercaptopyruvate sulfurtransferase level, and restoration of suramin-induced reduction in H2S synthesis in the kidneys. Suramin treatment exerted negligible effect on the RAS pathway in the adult male offspring kidneys. Our data suggested interplay among suramin, ADMA-NO pathway, and H2S synthesis pathway in programmed hypertension. Furthermore, NAC administration in pregnant rats with hypertension prevented programmed hypertension in adult offspring.

机译：成年高血压可以编程子痫前期。失衡血管活性的因素,包括氮氧化(没有)、硫化氢(H2S)肾素-血管紧张素系统(RAS)。是否(NAC)治疗母亲的防治作用预防孕产妇苏拉明treatment-induced编程高血压在后代和探索这种疗法的效果没有,硫化氢,RAS通路的肾脏。老鼠腹腔内注射60毫克/公斤苏拉明独自妊娠天10和11有或没有1% NAC治疗在整个怀孕和饮用水泌乳期。分成四组(n = 8 - 10 /组):控制,苏拉明、南汽和苏拉明+南汽。在12周的年龄后代被安乐死。孕产妇苏拉明治疗诱导编程高血压男性后代,这是预防孕产妇NAC治疗。高血压是Suramin-induced编程增加等离子体不对称的dimethylarginine (ADMA NO合酶抑制剂)水平,降低血浆L-arginine-to-ADMA比率,和减少肾dimethylargininedimethylaminohydrolase (ADMA-metabolizing酶)活性。针对suramin-induced编程高血压与等离子体的增加有关吗谷胱甘肽水平,增加肾3-mercaptopyruvate sulfurtransferase水平,恢复suramin-induced减少硫化氢合成的肾脏。施加在RAS途径的影响几乎可以忽略不计成年男性后代肾脏。建议ADMA-NO苏拉明之间的相互作用通路,在编程和硫化氢合成途径高血压怀孕的老鼠与高血压预防编程高血压在成年子女。

N-Acetylcysteine Prevents Programmed Hypertension in Male Rat Offspring Born to Suramin-Treated Mothers

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