ESTROGEN MODULATES CARDIAC REFLEX CONTROL OF VEINS

雌激素调节心脏的静脉反射控制

• 批准号: 2805762
• 负责人: DOUGLAS S MARTIN
• 金额: $ 9.75万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2001-10-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2805762
• 关键词: afferent nerve; baroreceptors; baroreflex; blood pressure; estrogens; female; gender difference; heart rate; hemodynamics; hormone regulation /control mechanism; laboratory rat; nitric oxide; nitric oxide synthase; paraventricular nucleus; vasomotion; veins

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.

描述：（改编自应用）静脉通过调节静脉回流、心脏预负荷、心输出量和心肌需氧量在心血管稳态中起重要作用。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，对静脉的心脏反射控制的研究相对较少。对狗的研究表明，心脏迷走神经传入通路引起静脉扩张和心脏充盈减少。此外，静脉张力的变化与心血管对冠状动脉缺血、充血性心力衰竭和心肌梗死的反应有关。因此，心脏反射控制静脉张力可能在心血管稳态中起重要作用。此外，雌激素被认为至少在一定程度上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来发挥心脏保护作用。最近的研究表明，雌性大鼠对交感神经活动的心脏反射控制增强，雌性保护心脏免受缺血。雌激素调节反射功能可能通过降低静脉回流、预负荷和心肌需氧量来保护缺血心脏。提出的研究将解决一般的假设：雌激素调节心脏传入反射控制静脉张力在有意识的大鼠。具体目的将是测试这一假设的三个预测：1)雌激素减轻心脏压力传入介导的静脉收缩。II)雌激素增强心脏抑制剂传入诱导的血管扩张。雌激素通过影响PVN调节心脏传入反射对静脉张力的控制。这些工作假设将通过测量平均动脉压、心率和平均循环充血压力（MCFP）来检验，MCFP是有意识大鼠综合静脉张力的指标。这些变量将分别通过心包注射缓激肽和血清素来监测心脏升压和降压传入。比较假手术、性腺切除或性腺切除+雌激素替代对雄性和雌性大鼠的反应，以评估雌激素的调节作用。我们将通过病变和显微注射实验来研究PVN的作用。为了确定一氧化氮是否参与雌激素效应，我们将在阻断一氧化氮合酶前后获得应答。这些研究有望证明，心脏传入控制外周运动性张力是由雌激素通过与一氧化氮的相互作用调节的。