An afferent explanation for sexual dimorphism in the aortic baroreflex of rat

Abstract

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.

Potentiation of 17β-estradiol on neuroexcitability by HCN-mediated neuromodulation of fast-afterhyperpolarization and late-afterdepolarization in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons via GPR30 in female rats

“…This novel finding demonstrates that I h is a key player not only in cardiac pacemaking during phase 4 spontaneous depolarization but also in baroreflex discharge facilitating during afterhyperpolarization of afferent neurons. Moreover, the 17β-E 2 -mediated potentiation is confirmed in neither myelinated A-nor unmyelinated C-types, which may explain at least partially that 17β-E 2 leads a relatively lower firing threshold and higher discharge capability of Ah-type BRNs [4] and retains a lower blood pressure in ovary intact female rats compared with aged-matched males upon baroreflex [2]. The I h -dependent potentiation has advanced our understanding from a basic and physiologically relevant concept to practical applications potentially valuable for clinical and therapeutical conditions.…”

“…17β-Estradiol (17β-E 2 ), as a female hormone, demonstrates a boarder role in modulating neuroexcitability of visceral afferent neurons [1], such as baroreceptor neurons (BRNs), hence, participating in the baroreflex function [2], the cellular and ion channel mechanisms involved in this function have always attracted the keen attention of investigators. A wealth of information indicates that 17β-E 2 enhances the excitability in both CNS neurons [3] and visceral afferent neurons including BRNs [4] by modification of expression profiles of hyperpolarizationactivated cyclic nucleotide-gated (HCN) channels [5] underlying the funny current (I f ) or hyperpolarization-activated current (I h ), which is originally described in sinoatrial node myocytes as an inward current activated on hyperpolarization to the diastolic range of voltages and has the capability for generating repetitive activity [6].…”

Human mesenchymal stem cells improve the neurodegeneration of femoral nerve in a diabetic foot ulceration rats

“…This experiment was conducted following the protocols described in details previously [13]. Briefly, 1.0-V and 15-V stimulus intensities were used to determine the fast (myelinated fiber activation, >2.0 M/s) and slow (unmyelinated fiber activation, <2.0 M/s) components of compound action potential (CAP), respectively.…”

Modeling the differentiation of A- and C-type baroreceptor firing patterns

“…This disorder occurs in five females for every one occurrence in males (Pickering (2002)). We speculate that this may be associated with different ratio of A- vs. Ah-fibers in males and females (see Li et al (2008); Chavez et al (2014)). …”

“…Another observation by Li et al (2008) from electrophysiological and anatomical studies in rats showed that A-type neurons may be separated into two subtypes A- and Ah-type, and that female rats have significantly more Ah-type neurons than male rats. Further studies by Chavez et al (2014) of these fibers have revealed that selective stimulation of myelinated neurons in female rats exhibits a lower threshold for MAP reduction compared to male rats suggesting that Ah-type baroreceptors may provide a functionally distinct afferent pathway within the baroreflex arc.…”