关键词: diabetes female nitric oxide oxidative stress renal microcirculation sex difference tubular transport

Mesh : Animals Diabetes Mellitus, Experimental / metabolism physiopathology Female Nitric Oxide / metabolism Male Adenosine / metabolism Rats Rats, Sprague-Dawley Kidney / metabolism Theophylline / pharmacology Hemodynamics Streptozocin Sex Characteristics NG-Nitroarginine Methyl Ester / pharmacology Blood Pressure / drug effects

来  源:   DOI:10.3390/ijms25147699   PDF(Pubmed)

Abstract:
Recently, we compared an interplay of the adenosine system and nitric oxide (NO) in the regulation of renal function between male normoglycaemic (NG) and streptozotocin-induced diabetic rats (DM). Considering the between-sex functional differences, e.g., in the NO status, we present similar studies performed in female rats. We examined if the theophylline effects (non-selective adenosine antagonist) in NG and DM females with or without active NO synthases differed from the earlier findings. In anaesthetised female Sprague Dawley rats, both NG and DM, untreated or after NO synthesis blockade with L-NAME, theophylline effects, on blood pressure, renal hemodynamics and excretion, and renal tissue NO were investigated. Renal artery blood flow (Transonic probe), cortical, outer-, and inner-medullary flows (laser-Doppler technique), and renal tissue NO signal (selective electrode) were measured. In contrast to males, in female NG and DM rats, theophylline induced renal vasodilation. In NO-deficient females, theophylline induced comparable renal vasodilatation, confirming the vasoconstrictor influence of the renal adenosine. In NG and DM females with intact NO synthesis, adenosine inhibition diminished kidney tissue NO, contrasting with an increase reported in males. Lowered baseline renal excretion in DM females suggested stimulation of renal tubular reabsorption due to the prevalence of antinatriuretic over natriuretic tubular action of adenosine receptors. An opposite inter-receptor balance pattern emerged previously from male studies. The study exposed between-sex functional differences in the interrelation of adenosine and NO in rats with normoglycaemia and streptozotocin diabetes. The findings also suggest that in diabetes mellitus, the abundance of individual receptor types can distinctly differ between females and males.
摘要:
最近,我们比较了腺苷系统和一氧化氮(NO)在调节雄性血糖正常(NG)和链脲佐菌素诱导的糖尿病大鼠(DM)肾功能中的相互作用。考虑到性别之间的功能差异,例如,在NO状态下,我们提出了在雌性大鼠中进行的类似研究。我们检查了在有或没有活性NO合酶的NG和DM雌性中的茶碱作用(非选择性腺苷拮抗剂)是否与先前的发现不同。在麻醉的雌性SpragueDawley老鼠中,NG和DM,未经处理或用L-NAME阻断NO合成后,茶碱的作用,关于血压,肾血流动力学和排泄,和肾组织NO进行了调查。肾动脉血流量(跨音速探头),皮质,outerness-,和髓内流(激光多普勒技术),测定肾组织NO信号(选择性电极)。与男性相比,在雌性NG和DM大鼠中,茶碱诱导肾血管舒张。在没有缺陷的女性中,茶碱可引起相当的肾血管舒张,确认肾腺苷的血管收缩作用。在NO合成完整的NG和DM雌性中,腺苷抑制减少肾组织NO,与男性报告的增加形成鲜明对比。DM女性的基线肾脏排泄降低表明,由于抗心房利尿剂的流行超过了腺苷受体的利钠肾小管作用,因此刺激了肾小管的重吸收。先前从男性研究中出现了相反的受体间平衡模式。该研究揭示了血糖正常和链脲佐菌素糖尿病大鼠中腺苷和NO相互关系的性别差异。研究结果还表明,在糖尿病中,个体受体类型的丰度在女性和男性之间可以明显不同。
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