Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats
Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats
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DOI：
10.1152/ajpheart.00499.2018
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Felder, Robert B.
中科院分区：
文献类型：
--
作者：
Yu, Yang;Wei, Shun-Guang;Felder, Robert B.
收缩期心力衰竭（HF）的表现、结果和治疗反应的性别差异已被报道。在本研究中，我们研究了性别对心衰大鼠神经体液兴奋及其周围表现的中枢神经机制的影响。雄性和雌性Sprague-Dawley大鼠冠状动脉结扎（CL）诱导HF。年龄匹配的大鼠作为对照。缺血区和左心室功能在术后24 h和4周相似。雌性心力衰竭大鼠死亡率较低，血流动力学损害较小。肺充血和右心室重构。两性HF大鼠血浆血管紧张素II （ANG II）、精氨酸加压素（AVP）和去甲肾上腺素水平均升高，但雌性大鼠血浆AVP和去甲肾上腺素水平升高较少。下丘脑室旁核是心衰中参与神经内分泌兴奋的关键心血管相关核。在下丘脑室旁核中，两性心衰大鼠炎症前细胞因子肿瘤坏死因子- α和白细胞介素-1 β以及环氧化酶-2和ANG II型la受体的mRNA水平均升高，但雌性大鼠较低。血管紧张素转换酶2蛋白水平在雌性HF大鼠中升高，而在雄性LIE大鼠中降低。对照组和HE组雌性大鼠AVP mRNA水平均低于各自的雄性组。在HF患者中，细胞外信号调节蛋白激酶1和2的激活在两性中相似地增加。结果表明，在初始缺血性心脏损伤程度相同的情况下，雌性HF大鼠的中枢神经兴奋程度和相关血流动力学损害程度均低于雄性HF大鼠。心衰（HF）的表现和治疗反应的性别差异已被广泛认识，但其潜在机制尚不清楚。本研究描述了在缺血性心衰中驱动神经体液兴奋的中枢神经系统机制的性别差异。雌性大鼠对HE的中枢神经化学反应较弱，血流动力学损害较小。性激素可能对心衰中枢和外周适应性的差异有贡献。
Sex differences in the presentation, outcome, and responses to treatment of systolic heart failure (HF) have been reported. In the present study, we examined the effect of sex on central neural mechanisms contributing to neurohumoral excitation and its peripheral manifestations in rats with HF. Male and female Sprague-Dawley rats underwent coronary artery ligation (CL) to induce HF. Age-matched rats served as controls. Ischemic zone and left ventricular function were similar 24 h and 4 wk after CL. Female rats with HF had a lower mortality rate and less hemodynamic compromise. pulmonary congestion, and right ventricular remodeling 4 wk after CL. Plasma angiotensin II (ANG II), arginine vasopressin (AVP), and norepinephrine levels were increased in HF rats in both sexes, but AVP and norepinephrine levels increased less in female rats. In the hypothalamic paraventricular nucleus, a key cardiovascular-related nucleus contributing to neurohumoral excitation in HF, mRNA levels for the prointlammatory cytokines tumor necrosis factor-alpha and interleukin-1 beta as well as cyclooxygenase-2 and the ANG II type la receptor were increased in HF rats of both sexes, but less so in female rats. Angiotensin-converting enzyme 2 protein levels increased in female HF rats but decreased in male LIE rats. mRNA levels of AVP were lower in female rats in both control and HE groups compared with the respective male groups. Activation of extracellular signal-regulated protein kinases 1 and 2 increased similarly in both sexes in HF. The results suggest that female HF rats have less central neural excitation and less associated hemodynamic compromise than male HF rats with the same degree of initial ischemic cardiac injury.NEW & NOTEWORTHY Sex differences in the presentation and responses to treatment of heart failure (HF) are widely recognized, but the underlying mechanisms are poorly understood. The present study describes sex differences in the central nervous system mechanisms that drive neurohumoral excitation in ischemia-induced HF. Female rats had a less intense central neurochemical response to HE and experienced less hemodynamic compromise. Sex hormones may contribute to these differences in the central and peripheral adaptations to HF.