The postmenopausal hot flash: cutaneous and hemodynamic mechanisms

绝经后潮热：皮肤和血液动力学机制

基本信息

批准号：
7569437
负责人：
CRAIG G CRANDALL
金额：
$ 15.15万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-02-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7569437
关键词：
Acute Affect Age Anxiety Beds Blood Pressure Blood Vessels Blood flow Community Healthcare Coupled Cutaneous Data Development Disodium Salt Nitroprusside Esthesia Estrogen Therapy Estrogens Fatigue Female Frequencies Frustration Heating Hormonal Hot flushes Hypotension Knowledge Lead Limb structure Measurement Mediating Menopause Microdialysis Muscarinic Acetylcholine Receptor Nausea Nerve Nitric Oxide Nitric Oxide Donors Nitric Oxide Synthase Physiological Postmenopause Quality of life Relative (related person)Reporting Sex Functioning Signal Transduction Skin Sleep Sweat Sweat Glands Sweating Symptoms System Techniques Testing Vasoconstrictor Agents Vasodilator Agents Withdrawal Woman Work base cholinergic depression experience hemodynamics innovation interest novel psychologic public health relevance relating to nervous system response

项目摘要

DESCRIPTION (provided by applicant): Hot flashes are a primary symptom of the female menopause that greatly impairs quality of life. Despite the considerable problem hot flashes pose for a large number of women, especially given decreased use of hormonal based therapies to treat hot flash symptoms, knowledge regarding the mechanisms of hot flash symptoms is greatly disproportional relative to the extent of the problem. The primary objective of this proposal is to examine mechanisms of cutaneous vascular, sweating, and systemic hemodynamic responses during hot flashes. The signal responsible for elevations in skin blood flow and sweating during a hot flash is not entirely clear and may be neural in origin. Using the innovative technique of multifiber recordings of postganglionic skin sympathetic nerve activity (SSNA) concurrently with skin blood flow and sweat rate measurements SPECIFIC AIM #1 will test the hypothesis that SSNA increases, concomitant with elevations in skin blood flow and sweating, during a hot flash and that the magnitude of the increase in SSNA is directly related to the magnitude of the rise in skin blood flow and sweating. Changes in skin blood flow during a hot flash may occur through modulation of: i) a sympathetic vasoconstrictor system, ii) a separate sympathetic cholinergic active vasodilator system, and/or iii) local factors related to nitric oxide (NO); while increases in sweating during a hot flash may occur upon excitation of cholinergic sympathetic nerves. SPECIFIC AIM #2 will test the hypothesis that withdrawal of sympathetic vasoconstrictor activity, increases in sympathetic cholinergic active vasodilator activity, and/or factors related to NO mediate increases in skin blood flow during a hot flash. Furthermore, this specific aim will test the hypothesis that sweating during a hot flash occurs through cholinergic sympathetic stimulation. These questions will be evaluated using the novel technique of intradermal microdialysis to locally deliver pharmacological agents coupled with continuous assessment of skin blood flow and sweating. In a subset of subjects blood pressure decreases during a hot flash, perhaps due to pronounced increases in cutaneous vascular conductance. Furthermore, symptoms of a hot flash have been reported to be similar to systemic sodium nitroprusside administration (an NO donor that increases cutaneous vascular conductance and lowers blood pressure). Together, these observations raise the possibility that symptoms of a hot flash may be associated with an "NO surge". Therefore, SPECIFIC AIM #3 will test the hypothesis that systemic inhibition of NO synthase reduces the frequency as well as magnitude of objective responses of hot flashes. Upon completion of the proposed work a greater understanding of pre- and post-synaptic mechanisms causing increases in skin blood flow and sweating during a hot flash will be obtained. Moreover, potential mechanisms that modulate blood pressure during hot flashes will be identified. These findings will provide vital information to the health care community that could aid in the development of non-hormonal treatments to decrease the frequency and ameliorate symptoms of hot flashes. Public Health Relevance Statement: Hot flashes are one of the most significant physiological symptoms of the female menopause that greatly impairs the quality of life. Despite the considerable problem hot flashes pose for a large number of women, especially given decreased use of hormonal based therapies to treat hot flash symptoms, relatively little is known regarding the mechanisms of these symptoms. The completion of the proposed work will provide important information regarding mechanisms of skin blood flow, sweating, and blood pressure responses during hot flashes to the health care community that could aid in the development of non-hormonal treatments to reduce hot flash frequency and related symptoms.

描述（由申请人提供）：潮热是女性更年期的主要症状，极大地损害了生活质量。尽管大量女性的潮热效果很大，但尤其是考虑到使用基于激素的疗法来治疗热闪光症状的使用降低，有关热闪光症状机制的知识与问题程度相对于问题的程度非常不好。该提案的主要目的是检查热闪光期间皮肤血管，出汗和全身血液动力学反应的机制。导致皮肤血流和热闪光期间出汗高程的信号尚不完全清楚，可能是神经的。使用跨移民后皮肤交感神经活动（SSNA）的创新技术与皮肤血流量和汗水速率测量同时，特定的目标＃1将测试SSNA增加的假说，同时增加了皮肤血液流动和出汗的高度，在炎热的闪光和流血的幅度上，ssnna的幅度是造成的。热闪光期间皮肤血流的变化可能通过：i）：i）交感神经血管收缩系统，ii）单独的交感神经能活性血管扩张器系统和/或iii）与一氧化氮有关的局部因素（no）；胆碱能交感神经激发时可能会在热闪烁过程中增加出汗。具体的目标＃2将检验以下假设：戒断交感神经能量活性，交感神经能活跃的血管扩张剂活性的增加和/或与无介导的因素相关的因素，在热闪光期间，皮肤血流的增加。此外，这个特定的目标将检验以下假设：在热闪光期间出汗是通过胆碱能交感神经刺激发生的。这些问题将使用新型的皮内微透析技术进行评估，以局部提供药理学剂，并连续评估皮肤血流和出汗。在受试者的一部分中，在热闪光期间，血压降低，这可能是由于皮肤血管电导的明显增加。此外，据报道，热闪光的症状类似于全身性硝普钠给药（无供体，可以增加皮肤血管电导并降低血压）。这些观察结果共同提出了一种可能与“无激增”有关的症状可能与之相关的可能性。因此，特定的目标＃3将检验以下假设：全身抑制无合酶会降低热闪光的频率和大小。提出的工作完成后，将获得对潮热后和突触后机制的更多了解，从而在热闪光期间增加皮肤血流和出汗。此外，将确定调节血压调节血压的潜在机制。这些发现将为医疗保健社区提供重要的信息，以帮助开发非激素治疗，以减少潮热的频率和改善症状。公共卫生相关性声明：潮热是女性更年期最重要的生理症状之一，极大地损害了生活质量。尽管有很多问题的热闪光对许多女性构成了姿势，尤其是由于使用基于激素的疗法治疗热闪光症状的使用降低，但对于这些症状的机制而言，相对较少知道。拟议工作的完成将提供有关皮肤血流，出汗和血压反应机制的重要信息，以便在卫生保健社区中闪烁，这可能有助于开发非激素治疗，以减少闪光灯频率和相关症状。