ESTROGEN MODULATES CARDIAC REFLEX CONTROL OF VEINS

描述：(改编自应用)静脉通过调节静脉回流、心脏前负荷、心输出量和心肌耗氧量，在心血管内稳态中发挥重要作用。静脉功能至少部分是通过动脉压力感受器反射来控制的。然而，静脉的心脏反射控制得到的研究相对较少。在狗身上的研究表明，心脏迷走神经传入通路会导致静脉扩张和心脏充盈减少。此外，静脉张力的变化与冠状动脉缺血、充血性心力衰竭和心肌梗死的心血管反应有关。因此，心脏反射对静脉张力的控制可能在心血管内稳态中发挥重要作用。此外，雌激素被认为至少部分地通过对血管平滑肌的直接作用、通过增强一氧化氮系统、通过与心血管反射的相互作用或通过对中枢神经系统的作用而发挥心脏保护作用。最近的研究表明，交感神经活动的心脏反射控制在雌性大鼠中得到加强，雌性大鼠保护心脏免受缺血。雌激素对反射功能的调节可能通过降低静脉回流、前负荷和心肌耗氧量来保护缺血心脏。这项拟议的研究将解决这样的普遍假设：雌激素调节清醒大鼠心脏传入反射对静脉张力的控制。具体目的将是检验这一假说的三个预测：i)雌激素减弱心脏加压神经传入介导的静脉收缩。Ii)雌激素增强心脏降压素传入引起的静脉扩张。3)雌激素通过作用于室旁核，调节心脏传入反射对静脉张力的控制。这些工作假说将通过测量平均动脉压、心率和平均循环充盈压(MCFP)来验证，MCFP是清醒大鼠综合毒液运动强度的指标。在心包注射缓激肽和5-羟色胺分别刺激心脏升压和降压传入神经的过程中，将监测这些变量。比较雄性和雌性大鼠在假手术、性腺切除或性腺切除+雌激素替代后的反应，将评估雌激素的调节作用。PVN的作用将通过损毁和微量注射实验来研究。为了确定一氧化氮是否参与雌激素的作用，我们将获得一氧化氮合酶阻断前后的反应。这些研究有望证明，心脏传入神经对外周毒液运动张力的控制是由雌激素通过与一氧化氮的相互作用来调节的。

DESCRIPTION: (Adapted from the application) Veins play an important role in cardiovascular homeostasis by modulating venous return, cardiac preload, cardiac output and myocardial oxygen demand. Venous function is controlled, at least in part, via the arterial baroreceptor reflexes. However, cardiac reflex control of veins has received comparatively little study. Studies in dogs suggest that cardiac vagal afferent pathways cause venodilation and a reduction in cardiac filling. Moreover, changes in venous tone are involved in the cardiovascular responses to coronary ischemia, congestive heart failure and myocardial infarction. Thus, cardiac reflex control of venous tone may play an important role in cardiovascular homeostasis. In addition, estrogen is thought to exert cardioprotective effects at least in part via direct effects on vascular smooth muscle, via potentiation of the nitric oxide system, via interaction with cardiovascular reflexes or via effects in the central nervous system. Recent studies suggest that cardiac reflex control of sympathetic nerve activity is enhanced in female rats and that female gender protects the heart from ischemia. Estrogen modulation of reflex function may serve to protect the ischemic heart by lowering venous return, preload and myocardial oxygen demand. The proposed research will address the general hypothesis that: Estrogen modulates cardiac afferent reflex control of venous tone in conscious rats. The specific aims will be test three predictions of this hypothesis: I) Estrogen attenuates cardiac pressor afferent mediated venoconstriction. II) Estrogen enhances cardiac depressor afferent induced venodilation. III) Estrogen modulates cardiac afferent reflex control of venous tone via an effect in the PVN. These working hypotheses will be tested by measuring mean arterial pressure, heart rate and mean circulatory filling pressure (MCFP), an index of integrated venomotor tone in conscious rats. These variables will be monitored during stimulation of cardiac pressor and depressor afferents by pericardial injection of bradykinin and serotonin respectively. Comparing responses in male and female rats subjected to sham surgery, gonadectomy or gonadectomy+estrogen replacement will assess the modulatory role of estrogen. The role of the PVN will be studied via lesion and microinjection experiments. In order to determine if nitric oxide is involved in the estrogenic effects, responses will be obtained before and after blockade of nitric oxide synthase. These studies are expected to demonstrate that cardiac afferent control of peripheral venomotor tone is modulated by estrogen via an interaction with nitric oxide.