Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana; Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, Indiana;
Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, Indiana;
Am J Physiol Heart Circ Physiol. 2014 Sep 15;307(6):H910-21. doi: 10.1152/ajpheart.00332.2014. Epub 2014 Jul 18.
Sex differences in baroreflex (BRx) function are well documented. Hormones likely contribute to this dimorphism, but many functional aspects remain unresolved. Our lab has been investigating a subset of vagal sensory neurons that constitute nearly 50% of the total population of myelinated aortic baroreceptors (BR) in female rats but less than 2% in male rats. Termed "Ah," this unique phenotype has many of the nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type BR afferents. In this study, we utilize three distinct experimental protocols to determine if Ah-type barosensory afferents underlie, at least in part, the sex-related differences in BRx function. Electron microscopy of the aortic depressor nerve (ADN) revealed that female rats have less myelin (P < 0.03) and a smaller fiber cross-sectional area (P < 0.05) per BR fiber than male rats. Electrical stimulation of the ADN evoked compound action potentials and nerve conduction profiles that were markedly different (P < 0.01, n = 7 females and n = 9 males). Selective activation of ADN myelinated fibers evoked a BRx-mediated depressor response that was 3-7 times greater in female (n = 16) than in male (n = 17) rats. Interestingly, the most striking hemodynamic difference was functionally dependent upon the rate of myelinated barosensory fiber activation. Only 5-10 Hz of stimulation evoked a rapid, 20- to 30-mmHg reduction in arterial pressure of female rats, whereas rates of 50 Hz or higher were required to elicit a comparable depressor response from male rats. Collectively, our experimental results are suggestive of an alternative myelinated baroreceptor afferent pathway in females that may account for, at least in part, the noted sex-related differences in autonomic control of cardiovascular function.
性别对压力反射(BRx)功能的影响已有充分的记录。激素可能对此二态性有贡献,但许多功能方面仍未得到解决。我们的实验室一直在研究一类迷走感觉神经元,它们构成了雌性大鼠中几乎 50%的有髓质主动脉压力感受器(BR),但在雄性大鼠中不到 2%。这种独特的表型被称为“Ah”,具有有髓质 A 型和无髓质 C 型 BR 传入纤维的许多非重叠的电生理特性和化学敏感性。在这项研究中,我们利用三种不同的实验方案来确定 Ah 型压力感受器传入纤维是否至少部分地导致了 BRx 功能的性别差异。主动脉减压神经(ADN)的电子显微镜显示,雌性大鼠的每根 BR 纤维的髓鞘(P < 0.03)和纤维横截面积(P < 0.05)都比雄性大鼠小。ADN 的电刺激诱发的复合动作电位和神经传导曲线明显不同(P < 0.01,n = 7 只雌性和 n = 9 只雄性)。ADN 有髓纤维的选择性激活诱发了一种 BRx 介导的降压反应,在雌性(n = 16)比雄性(n = 17)大鼠中要大 3-7 倍。有趣的是,最显著的血流动力学差异在功能上依赖于有髓压力感受器纤维的激活速度。只有 5-10 Hz 的刺激会引起雌性大鼠动脉压快速下降 20-30 mmHg,而 50 Hz 或更高的刺激速率才会引起雄性大鼠产生类似的降压反应。总的来说,我们的实验结果提示,女性可能存在一种替代的有髓质压力感受器传入途径,至少部分解释了自主控制心血管功能的性别差异。