血压神经调控性别差异的关键:Ah型髓鞘化压力感受器神经元

Key player in neurocontrol of blood pressure regulation:myelinated Ah-type baroreceptor neuro

大量基础与临床的统计学结果表明,无论是正常血压还是高血压的发病率,成年男性均明显高于同龄女性,这种性别差异在绝经期后消失。我们经过近20年的研究发现,成年雌性大鼠结状神经节及孤束核中不仅分布有传统分类的髓鞘化A型和非髓鞘化C型内脏感觉/压力感受器神经元以外,还特异性分布一种髓鞘化Ah型神经元,它的电生理学特性、化学敏感性以及离子通道表达均与A型和C型有所不同。在体和离体研究结果显示,Ah型神经元具有以下功能特征:①仅分布于成年雌性大鼠,神经兴奋性依赖于雌激素的存在;②属于髓鞘化纤维,传导速度室温下2~20 m·s^-1,但动作电位复极期有类似于C型驼峰切记;③动作电位除极阈值、除极速度、动作电位时程以及放电频率均不同于A和C型;④同为髓鞘化纤维,Ah型对神经递质和血管活性物质敏感;⑤虽表现有除极期驼峰,Ah型对辣椒素不敏感,同工凝集素B4表达阴性;⑥Ah型功能性表达Nav1.7,Nav1.8和Nav1.9;⑦Ah型对血管紧张素Ⅱ高度敏感,并高表达血管紧张素Ⅱ型受体,参与降压作用;⑧Ah型对血清素高度敏感,可能与其高表达血清素Ⅲ型受体有关,下行抑制心脏疼痛感受,参与无痛心绞痛的发病过程;⑨Ah型对组胺高度敏感,并高表达组胺Ⅱ型受体,与哮喘发病的性别差异密切相关。综上所述,成年雌性大鼠髓鞘化Ah型内脏感觉神经元/压力感受器神经元,独立存在并不同于A和C型,是构成与内脏感觉/主动脉压力反射传入通路性别差异相关生理功能的神经解剖学基础,为合理解释上述相关病理生理机制揭开了新的一页。

A large body of statistical evidence collected from basic and clinical studies has demonstrated that not only the rate of normal blood pressure but also the incidence of hypertension observed in premenopausal women are lower than those in age-matched men and this gender difference disappears at the post-menopausal age. During the past two decades, we have discovered female-specific subpopulation of myelinated Ah-type baroreceptor/baroreceptive neurons in the baroreflex afferent pathway including the nodose ganglia(NG) and nucleus tractus solitarius(NTS), besides traditionally classified myelinated A-and unmyelinated C-types, that show significant electrophysiological characteristics, chemosensitivity and ion channel expression compared with A-and C-types. In vivo and vitro studies have shown that Ah-type neurons possess the following characteristics: ① Ah-types are discovered only in adult female rats and their neuroexcitability is estrogen-dependent;② Ah-types belong to myelinated afferents with faster conduction ranging from 2 to 20 m·s-1 at room temperature with C-typelike repolarization hump;③ the threshold, rate of depolarization, and duration of action potential, as well as the repetitive property differ significantly from A-and C-types;④ as myelinated afferents,Ah-types respond to almost all sorts of neurotransmitters and vasoactive agents;⑤ even with a repolarization hump, Ah-types are insensitive to capsaicin with negative expression of isolectin-B4;⑥ Ah-types functionally express voltage-gate Na+channels including Nav1.7, Nav1.8, and Nav1.9;⑦ higher sensitivity to Angiotensin-Ⅱ and higher expression of the type-Ⅱ receptor of angiotensin-Ⅱ play a critical role in hypotensive action;⑧ higher sensitivity to serotonin and higher expression of its type-Ⅲ receptor play a descending inhibition on cardiac nociception leading presumably to salient angina;⑨ higher sensitivity to histamine and higher expression of the type-Ⅱ receptor are the potential mechanism for sexual-dimorphism of the prevalence of asthma. Taken all these data together, we conclude that myelinated Ah-type visceral sensory and baroreceptor/baroreceptive neurons identified in the NG/NTS of adult female rats are newly discovered neuron types that differ from traditionally classified myelinated A-and unmyelinated C-types, and this discovery will facilitate neuroanatomy for the sexual dimorphisms of visceral/baroreflex afferent function and may usher a new era for understanding the genderrelated pathophysiological mechanisms.