The female gender is protected against immunological complications of endotoxemia. Here we investigated whether gonadal hormone depletion by ovariectomy (OVX) uncovers inflammatory and cardiovascular effects of endotoxemia and whether these effects are reversed by hormone replacement therapies. Changes in inflammatory cytokines, blood pressure (BP), left ventricular (LV) function, and cardiac autonomic activity caused by lipopolysaccharide (LPS) in conscious female rats with different hormonal states were determined. In contrast to no effects in sham-operated females, treatment of OVX rats with LPS (i) decreased BP, (ii) increased spectral low-frequency/high-frequency ratio of HRV, denoting enhanced cardiac sympathetic dominance, (iii) attenuated reflex tachycardic responses to sodium nitroprusside, and (iv) increased systolic contractility (dP/dt_max). The developed hypotension was (i) fully eliminated in estrogen (E₂)-pretreated OVX rats, (ii) partially counteracted after selective activation of estrogen receptor-α (PPT) or β (DPN). All estrogenic compounds abrogated LPS enhancement of cardiac sympathetic drive. However, PPT was more successful than E2 or DPN in compromising LPS depression in baroreflex activity and elevation in dP/dt_max. Molecular studies showed that PPT was most effective in attenuating the upregulated myocardial expressions of NF-κB and iNOS in endotoxic OVX rats. Myocardial expression of the defensive HSP70 was comparably increased by all estrogenic products. Except for improved cardiac spectral activity, none of these functional or molecular entities was affected by medroxyprogesterone acetate (MPA). Overall, our data suggest diverse therapeutic advantages for gonadal hormones in the worsened endotoxic complications in rats with surgical menopause, with probably more favorable role for ERα agonism within this context.

保护女性免受内毒素血症的免疫并发症的侵害。在这里，我们调查了通过卵巢切除术（OVX）进行的性腺激素耗竭是否能揭示内毒素血症的炎症和心血管作用，以及激素替代疗法是否可以逆转这些作用。确定在不同荷尔蒙状态的清醒雌性大鼠中，脂多糖（LPS）引起的炎症细胞因子，血压（BP），左心室（LV）功能和心脏自主神经活动的变化。与假手术雌性小鼠无影响相比，用LPS治疗OVX大鼠（i）降低血压，（ii）HRV的低频/高频比增加，表示心脏交感优势增强，（iii）反射减弱对硝普钠的心动过速反应，以及（iv）收缩压增加（dP / dt_最高）。（i）在雌激素（E ₂）预处理的OVX大鼠中完全消除了低血压，（ii）在选择性激活雌激素受体-α（PPT）或β（DPN）后部分抵消了低血压。所有雌激素化合物均废除了LPS增强的心脏交感神经驱动力。然而，在减轻压力反射活动中的LPS抑制和dP / dt _max升高方面，PPT比E2或DPN更成功。。分子研究表明，PPT在减轻内毒素性OVX大鼠心肌中NF-κB和iNOS的表达上最有效。所有雌激素产物相比，防御性HSP70的心肌表达均增加。除了改善的心脏频谱活动外，这些功能或分子实体均不受醋酸甲羟孕酮（MPA）的影响。总的来说，我们的数据表明，在更年期手术的大鼠中，性腺激素在恶化的内毒素并发症中具有多种治疗优势，在这种情况下，可能更有利于ERα激动作用。