Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats
Endoplasmic reticulum stress in the brain subfornical organ contributes to sex differences in angiotensin-dependent hypertension in rats
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DOI：
10.1111/apha.12635
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发表时间：
2016-05-01
影响因子：
6.3
通讯作者：
Peng, W.
中科院分区：
文献类型：
--
作者：
Dai, S. -Y.;Fan, J.;Peng, W.
脑穹窿下器官（SFO）是一个重要的心血管调节中心，其内质网（ER）应激与血管紧张素II（ANG）诱导的男性高血压有关;然而，ER应激对血管紧张素II诱导的女性高血压的作用尚不清楚。雌性激素已被证明可以防止外周的ER应激。我们测试的假设，女性是不太容易ANG II诱导的SFO ER压力比男性，导致高血压的性别差异。MethodsMale，完整和卵巢切除（OVX）的雌性大鼠接受了连续2周的皮下输注ANG II或生理盐水。额外的男性，完整的和OVX雌性大鼠接受脑室内（ICV）注射ER应激诱导剂衣霉素tunicamycin.ResultsANG II，但不是生理盐水，增加血压（BP）在男性和女性，但完整的女性表现出较小的增加BP和降压反应神经节阻滞相比，男性或OVX女性。分子研究表明，ANG II增加了男性和女性SFO中ER应激生物标志物的表达和Fra样活性;然而，完整女性中这些参数的升高低于男性或OVX女性。此外，ICV衣霉素诱导较小的血压升高和ER应激生物标志物在SFO中的表达增加较少的完整的女性相比，男性或OVX feminal.ConclusionThe结果表明，ANG II诱导的脑ER应激的差异，男性和女性之间的ANG II介导的高血压的性别差异，雌激素保护女性对ANG II诱导的脑ER应激。
AimEndoplasmic reticulum (ER) stress in the brain subfornical organ (SFO), a key cardiovascular regulatory centre, has been implicated in angiotensin (ANG) II-induced hypertension in males; however, the contribution of ER stress to ANG II-induced hypertension in females is unknown. Female hormones have been shown to prevent ER stress in the periphery. We tested the hypothesis that females are less susceptible to ANG II-induced SFO ER stress than males, leading to sex differences in hypertension.MethodsMale, intact and ovariectomized (OVX) female rats received a continuous 2-week subcutaneous infusion of ANG II or saline. Additional male, intact and OVX female rats received intracerebroventricular (ICV) injection of ER stress inducer tunicamycin.ResultsANG II, but not saline, increased blood pressure (BP) in both males and females, but intact females exhibited smaller increase in BP and less depressor response to ganglionic blockade compared with males or OVX females. Molecular studies revealed that ANG II elevated expression of ER stress biomarkers and Fra-like activity in the SFO in both males and females; however, elevations in these parameters were less in intact females than in males or OVX females. Moreover, ICV tunicamycin induced smaller elevation in BP and less increase in expression of ER stress biomarkers in the SFO in intact females compared with males or OVX females.ConclusionThe results suggest that differences in ANG II-induced brain ER stress between males and females contribute to sex differences in ANG II-mediated hypertension and that oestrogen protects females against ANG II-induced brain ER stress.