Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring.
Enhanced mesenteric arterial responsiveness to angiotensin II is androgen receptor-dependent in prenatally protein-restricted adult female rat offspring.
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在产前蛋白质限制的成年雌性大鼠后代中，肠系膜动脉对血管紧张素 II 的反应性增强是雄激素受体依赖性的。
DOI：
10.1095/biolreprod.114.126482
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发表时间：
2015
影响因子：
3.6
通讯作者：
Yallampalli,Chandrasekhar
中科院分区：
文献类型：
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作者：
Sathishkumar,Kunju;Balakrishnan,MeenaP;Yallampalli,Chandrasekhar
妊娠期蛋白限制导致成年雌性生长受限大鼠宫内生长受限和高血压。观察到血管对血管紧张素II的反应性增强，阻断肾素-血管紧张素系统可消除成年生长受限大鼠的高血压，提示肾素-血管紧张素系统有助于宫内生长受限诱导的高血压。此外，生长受限的成年大鼠血浆睾酮水平较高，抗雄激素治疗可消除高血压，表明睾酮的重要作用。我们假设雄激素可能在增强对Ang II和高血压的反应性中起关键作用。在6月龄时，用20%蛋白质（对照）或6%蛋白质（限制蛋白质）喂养怀孕大鼠的雌性后代。血浆睾酮和平均动脉压与对照组相比显著升高。氟他胺治疗（10 mg/kg/天皮下注射，持续10天）降低了蛋白质限制后代的平均动脉压，但在对照组中没有显著效果。在蛋白质受限的后代中，血管agtr1 / agtr2比值显著升高，氟他胺逆转了这一效应。氟他胺治疗对对照组agtr1 / agtr2比值无影响。与对照组相比，在蛋白限制的后代中观察到肠系膜动脉对血管紧张素II的收缩反应增强。氟他胺治疗逆转了蛋白限制后代对血管紧张素II增强的收缩反应，在对照组中没有显著效果。在接受氟他胺治疗和未接受氟他胺治疗的对照组和蛋白质限制后代之间，血管对苯肾上腺素的反应性相似，这表明增强的收缩反应和氟他胺的逆转作用是血管紧张素II所特有的。这些结果表明，产前蛋白受限大鼠对睾酮依赖性的血管紧张素II表现出增强的反应性。
Gestational protein restriction results in intrauterine growth restriction and hypertension in adult female growth-restricted rats. Enhanced vascular responsiveness to angiotensin II is observed, and blockade of the renin-angiotensin system abolishes hypertension in adult growth-restricted rats, suggesting that the renin-angiotensin system contributes to intrauterine growth restriction-induced hypertension. Moreover, growth-restricted adult rats have higher plasma testosterone levels, and antiandrogen treatment abolishes hypertension, indicating an important role for testosterone. We hypothesized that androgens may play a pivotal role in the enhanced responsiveness to Ang II and hypertension. Female offspring of pregnant rats fed 20% protein (control) or 6% protein diet (protein restricted), at 6 mo of age, were studied. Plasma testosterone and mean arterial pressure in protein-restricted offspring were significantly higher compared to controls. Flutamide treatment (10 mg/kg/day subcutaneously for 10 days) reduced mean arterial pressure in protein-restricted offspring but was without significant effect in controls. VascularAgtr1/Agtr2ratio was significantly higher in protein-restricted offspring, an effect that was reversed by flutamide. Flutamide treatment did not have any effect onAgtr1/Agtr2ratio in controls. Enhanced contractile response to angiotensin II in mesenteric arteries was observed in protein-restricted offspring compared with control. Flutamide treatment reversed the enhanced contractile response to angiotensin II in protein-restricted offspring without significant effect in controls. Vascular reactivity to phenylephrine was similar between the control and protein-restricted offspring with and without flutamide treatment, suggesting that enhanced contractile response and flutamide's reversal effect is specific to angiotensin II. These results suggest that prenatally protein-restricted rats exhibit an enhanced responsiveness to angiotensin II that is testosterone-dependent.