Natriuretic peptides (NPs) induce vasodilation, natriuresis, and diuresis, counteract the renin–angiotensin–aldosterone system and autonomic nervous system, and are key regulators of cardiovascular volume and pressure homeostasis. Baroreflex afferent pathway is an important reflex loop in the neuroregulation of blood pressure (BP), including nodose ganglion (NG) and nucleus tractus solitarius (NTS). Dysfunction of baroreflex would lead to various hypertensions. Here, we carried out functional experiments to explore the effects of NPs on baroreflex afferent function. Under physiological and hypertensive condition (high-fructose drinking-induced hypertension, HFD), BP was reduced by NPs through NG microinjection and baroreflex sensitivity (BRS) was enhanced via acute intravenous NPs injection. These anti-hypertensive effects were more obvious in female rats with the higher expression of NPs and its receptor A/B (NPRA/NPRB) and lower expression of its receptor C (NPRC). However, these effects were not as obvious as those in HFD rats compared with the same gender control group, which is likely to be explained by the abnormal expression of NPs and NPRs in the hypertensive condition. Our data provide additional evidence showing that NPs play a crucial role in neurocontrol of BP regulation via baroreflex afferent function and may be potential targets for clinical management of metabolic-related hypertension.
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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