Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation

Xu, Wenchang; Yu, Jun; Feng, Yan; Yan, Qiu‐Xin; Li, Xinyu; Liu, Ying; Liu, Zhuo; Wang, Di; Sun, Xun; Li, Kexin; Wang, Lu‐Qi; Qiao, Guofu; Li, Bai‐Yan

doi:10.1111/cns.13039

Cited by 9 publications

(4 citation statements)

References 46 publications

(123 reference statements)

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“…From an anatomical standpoint, the ADN in normotensive female rats shows less axonal myelination and smaller cross-sectional area compared with males, and females further express a unique population of low-threshold slow-conducting myelinated afferents known as Ah-type afferents [30,31]. These afferents have nonoverlapping electrophysiological properties and chemical sensitivities of both myelinated A-type and unmyelinated C-type baroreceptor afferents [30,31] and specifically display greater frequency and larger amplitude of spontaneous excitatory postsynaptic currents compared with inhibitory postsynaptic currents [32]. Specific to male and female SHRs, the persistent hypertensive state is commonly associated with smaller myelinated (A-type) and unmyelinated (C-type) axonal cross-sectional area within the ADN, thinner myelin sheath around myelinated axons, and smaller number of unmyelinated fibers in both male and female SHRs relative to normotensive controls [33][34][35], and while morphological and functional characteristics of Ah-type afferent fibers have never been studied in female SHRs, it is possible that similar pathological changes in this fiber subset may underlie the abrogated laterization phenomenon in female SHRs.…”

Section: Discussionmentioning

confidence: 99%

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats

Salman

2023

Journal of Hypertension

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Background: Altered baroreflex function is well documented in hypertension; however, the female sex remains far less studied compared with males. We have previously demonstrated a left-sided dominance in the expression of aortic baroreflex function in male spontaneously hypertensive rats (SHRs) and normotensive rats of either sex. If lateralization in aortic baroreflex function extends to hypertensive female rats remains undetermined. This study, therefore, assessed the contribution of left and right aortic baroreceptor afferents to baroreflex modulation in female SHRs. Method: Anesthetized female SHRs (total n = 9) were prepared for left, right and bilateral aortic depressor nerve (ADN) stimulation (1–40 Hz, 0.2 ms, 0.4 mA for 20 s) and measurement of reflex mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR) and femoral vascular resistance (FVR). All rats were also matched for the diestrus phase of the estrus cycle. Results: Reflex (%) reductions in MAP, HR, MVR and FVR were comparable for both left-sided and right-sided stimulation. Bilateral stimulation evoked slightly larger (P = 0.03) reductions in MVR compared with right-sided stimulation; however, all other reflex hemodynamic measures were similar to both left-sided and right-sided stimulation. Conclusion: These data show that female SHRs, unlike male SHRs, express similar central integration of left versus right aortic baroreceptor afferent input and thus show no laterization in the aortic baroreflex during hypertension. Marginal increases in mesenteric vasodilation following bilateral activation of the aortic baroreceptor afferents drive no superior depressor responses beyond that of the unilateral stimulation. Clinically, unilateral targeting of the left or right aortic baroreceptor afferents may provide adequate reductions in blood pressure in female hypertensive patients.

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Section: Discussionmentioning

confidence: 99%

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats

Salman

2023

Journal of Hypertension

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“…The results from qRT-PCR and western blot analysis showed that VEGF mechanosensitive channels (PIEZONs) [26] at baroreceptor terminals of aorta, the converted action potential discharge (bioelectric signals ) from the blood pressure changes (mechanical signals) can be propagated to the 1st-order baroreceptor neurons with the cell bodies housed in the NG [27][28]. The signals are then relayed through their central projections to the medial NTS [29][30][31]…”

Section: Expression Alterations Of Vegf/vegfrs In the Kidney Of Rvh Ratsmentioning

confidence: 99%

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Feng

Yang

et al. 2021

Frigid Zone Medicine

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Objective Oncocardiology is increasingly hot research field/topic in the clinical management of cancer with anti-angiogenic therapy of vascular endothelial growth factor (VEGF) that may cause cardiovascular toxicity, such as hypertension via vascular dysfunction and attenuation of eNOS/NO signaling in the baroreflex afferent pathway. The aim of the current study was to evaluate the potential roles of VEGF/VEGF receptors (VEGFRs) expressed in the baroreflex afferent pathway in autonomic control of blood pressure (BP) regulation. Methods The distribution and expression of VEGF/VEGFRs were detected in the nodose ganglia (NG) and nucleus of tractus solitary (NTS) using immunostaining and molecular approaches. The direct role of VEGF was tested by NG microinjection under physiological and hypertensive conditions. Results Immunostaining data showed that either VEGF or VEGFR2/VEGFR3 was clearly detected in the NG and NTS of adult male rats. Microinjection of VEGF directly into the NG reduced the mean blood pressure (MBP) dose-dependently, which was less dramatic in renovascular hypertension (RVH) rats, suggesting the VEGF-mediated depressor response by direct activation of the 1st-order baroreceptor neurons in the NG under both normal and disease conditions. Notably, this reduced depressor response in RVH rats was directly caused by the downregulation of VEGFR2, which compensated the up regulation of VEGF/VEGFR3 in the NG during the development of hypertension. Conclusion It demonstrated for the first time that the BP-lowering property of VEGF/VEGFRs signaling via the activation of baroreflex afferent function may be a common target/pathway leading to BP dysregulation in anti-angiogenic therapy.

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“…The autonomic nerve system (ANS) is the key player in the blood pressure (BP) homeostasis via the balance between sympathetic (cardiac afferents) and parasympathetic (vagal afferents), in which vagal inputs dominate this balance by rendering negatively feedback reflexed control mechanism, the baroreflex (BRx) plays a major role in the neurocontrol of both short‐term and long‐term BP regulation. BRx afferent loop initiates the sensing BP fluctuation by baroreceptor terminals distributed in the aorta 1 operated by mechanosensitive PIEZOs channels 2 , 3 , 4 to the cell body of the 1 st ‐order neurons 5 , 6 in the nodose ganglia (NG), and then to the cell body of the 2 nd ‐order neurons 7 , 8 in the nucleus tractus solitarius (NTS) by forming the synapses through its central projection and the efferent loop innervates to the heart and blood vessel. Extensive animal studies have demonstrated that BRx afferent function is critical to stabilize the BP under physiological and hypertensive conditions, 7 , 9 , 10 , 11 , 12 , 13 , 14 suggesting that dysfunction of BRx afferent function is crucial for the development of both primary and secondary hypertension.…”

Section: Introductionmentioning

confidence: 99%

“…BRx afferent loop initiates the sensing BP fluctuation by baroreceptor terminals distributed in the aorta 1 operated by mechanosensitive PIEZOs channels 2 , 3 , 4 to the cell body of the 1 st ‐order neurons 5 , 6 in the nodose ganglia (NG), and then to the cell body of the 2 nd ‐order neurons 7 , 8 in the nucleus tractus solitarius (NTS) by forming the synapses through its central projection and the efferent loop innervates to the heart and blood vessel. Extensive animal studies have demonstrated that BRx afferent function is critical to stabilize the BP under physiological and hypertensive conditions, 7 , 9 , 10 , 11 , 12 , 13 , 14 suggesting that dysfunction of BRx afferent function is crucial for the development of both primary and secondary hypertension.…”

Section: Introductionmentioning

confidence: 99%

Bradykinin‐mediated estrogen‐dependent depressor response by direct activation of female‐specific distribution of myelinated Ah‐type baroreceptor neurons in rats

Feng

Fan

et al. 2021

CNS Neurosci Ther

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Aim To understand the direct impact of bradykinin in autonomic control of circulation through baroreflex afferent pathway. Methods The mean arterial pressure (MAP) was monitored while bradykinin and its agonists were applied via nodose (NG) microinjection, the expression of bradykinin receptors (BRs) in the NG (1st‐order) and nucleus tractus solitarius (NTS, 2nd‐order) were tested in adult male, age‐matched female, and ovariectomized rats under physiological and hypertensive conditions. Additionally, bradykinin‐induced depolarization was also tested in identified baroreceptor and baroreceptive neurons using whole‐cell patch‐clamp technique. Results Under physiological condition, bradykinin‐induced dose‐ and estrogen‐dependent reductions of MAP with lower estimated EC50 in females. B2R agonist mediated more dramatic MAP reduction with long‐lasting effect compared with B1R activation. These functional observations were consistent with the molecular and immunostaining evidences. However, under hypertensive condition, the MAP reduction was significantly less dramatic in N’‐Nitro‐L‐Arginine‐methyl ester (L‐NAME) induced secondary and spontaneous hypertension rats in males compared with female rats. Electrophysiological data showed that bradykinin‐elicited concentration‐dependent membrane depolarization with discharges during initial phase in identified myelinated Ah‐types baroreceptor neurons, not myelinated A‐types; while, higher concentration of bradykinin was required for depolarization of unmyelinated C‐types without initial discharges. Conclusion These datasets have demonstrated for the first time that bradykinin mediates direct activation of baroreflex afferent function to trigger estrogen‐dependent depressor response, which is due mainly to the direct activation/neuroexcitation of female‐specific myelinated Ah‐type baroreceptor neurons leading to a sexual dimorphism in parasympathetic domination of blood pressure regulation via activation of B2R/B1R expression in baroreflex afferent pathway.

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Spontaneous activities in baroreflex afferent pathway contribute dominant role in parasympathetic neurocontrol of blood pressure regulation

Abstract: The data from current investigations establish a new concept for the role of Ah-type baroreceptor/baroreceptive neurons in controlling blood pressure stability and provide a new pathway for pharmacological intervention for hypertension and cardiovascular diseases.

Cited by 9 publications

References 46 publications

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats

Functional symmetry of the aortic baroreflex in female spontaneously hypertensive rats

Direct evidence of VEGF-mediated neuroregulation and afferent explanation of blood pressure dysregulation during angiogenic therapy

Bradykinin‐mediated estrogen‐dependent depressor response by direct activation of female‐specific distribution of myelinated Ah‐type baroreceptor neurons in rats

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