The postmenopausal hot flash: cutaneous and hemodynamic mechanisms

绝经后潮热：皮肤和血液动力学机制

• 批准号: 7386350
• 负责人: CRAIG G CRANDALL
• 金额: $ 18.9万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7386350
• 关键词: Acute; Affect; Age; Anxiety; Beds; Blood Pressure; Blood Vessels; Blood flow; Cholinergic Agents; Community Healthcare; Coupled; Cutaneous; Data; Development; Disodium Salt Nitroprusside; Elevation; Esthesia; Estrogen Therapy; Estrogens; Fatigue; Female; Frequencies; Frustration; Heating; Hormonal; Hot flushes; Hypotension; Knowledge; Lead; Limb structure; Measurement; Mediating; Menopausal hot flushes; Menopause; Mental Depression; Microdialysis; Muscarinic Acetylcholine Receptor; Nausea; Nerve; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Numbers; Physiological; Postmenopause; Public Health; Quality of life; Rate; Relative (related person); Reporting; Sex Functioning; Signal Transduction; Skin; Sleep; Sweat; Sweat Glands; Sweating; Symptoms; Synapses; System; Techniques; Testing; Vasoconstrictor Agents; Vasodilator Agents; Withdrawal; Woman; Work; base; cholinergic; experience; hemodynamics; innovation; interest; novel; psychologic; relating to nervous system; response

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，严重影响生活质量。尽管潮热给大量女性带来了相当大的问题，特别是考虑到治疗潮热症状的激素疗法的使用减少，但相对于问题的严重程度，有关潮热症状机制的知识却远远不成比例。该提案的主要目的是检查潮热期间皮肤血管、出汗和全身血流动力学反应的机制。潮热期间皮肤血流量增加和出汗的信号尚不完全清楚，可能是神经源性的。使用多纤维记录节后皮肤交感神经活动 (SSNA) 的创新技术，同时测量皮肤血​​流量和出汗率，具体目标 #1 将检验以下假设：在炎热天气下，SSNA 会增加，同时皮肤血流量和出汗率也会增加。闪光，SSNA 增加的幅度与皮肤血流量和出汗的增加幅度直接相关。潮热期间皮肤血流量的变化可能通过以下调节发生：i) 交感血管收缩系统，ii) 单独的交感胆碱能主动血管舒张系统，和/或 iii) 与一氧化氮 (NO) 相关的局部因素；而潮热期间出汗增加可能是由于胆碱能交感神经的兴奋而发生的。具体目标#2将检验以下假设：交感血管收缩活性的减弱、交感胆碱能活性血管舒张活性的增加和/或与NO相关的因素介导潮热期间皮肤血流量的增加。此外，这一具体目标将检验以下假设：潮热期间出汗是通过胆碱能交感神经刺激发生的。这些问题将使用皮内微透析新技术进行评估，以局部输送药物，并持续评估皮肤血流和出汗。在一部分受试者中，潮热期间血压会下降，这可能是由于皮肤血管电导率显着增加所致。此外，据报道，潮热的症状与全身硝普钠（一种增加皮肤血管传导性和降低血压的一氧化氮供体）相似。总之，这些观察结果提出了潮热症状可能与“一氧化氮激增”相关的可能性。因此，SPECIFIC AIM #3 将检验这样的假设：NO 合酶的全身抑制会降低潮热客观反应的频率和幅度。完成拟议的工作后，将对导致潮热期间皮肤血流量和出汗增加的突触前和突触后机制有更深入的了解。此外，还将确定潮热期间调节血压的潜在机制。这些发现将为医疗保健界提供重要信息，有助于开发非激素治疗方法，以减少潮热的频率并改善潮热症状。 公共卫生相关性声明：潮热是女性更年期最显着的生理症状之一，严重损害生活质量。尽管潮热给大量女性带来了相当大的问题，特别是考虑到治疗潮热症状的激素疗法的使用减少，但对于这些症状的机制知之甚少。拟议工作的完成将为医疗保健界提供有关潮热期间皮肤血流、出汗和血压反应机制的重要信息，这可能有助于开发非激素治疗方法，以减少潮热频率和相关症状。