Open AccessBradykinin‐mediated estrogen‐dependent depressor response by direct activation of female‐specific distribution of myelinated Ah‐type baroreceptor neurons in rats
Author(s) -
Li KeXin,
Feng Yan,
Fan XiongXiong,
Sun Xun,
Li Ying,
Wu Di,
Liu Li,
Cui ChangPeng,
Xiong Xue,
Li HuDie,
Zhou Meng,
Ma HaiLan,
Liu Yang,
Zhang Rong,
Li BaiYan
Publication year - 2022
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13792
Subject(s) - bradykinin , baroreceptor , baroreflex , endocrinology , medicine , chemistry , solitary nucleus , depolarization , phenylephrine , receptor , blood pressure , heart rate
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 (1 st ‐order) and nucleus tractus solitarius (NTS, 2 nd ‐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 EC 50 in females. B 2 R agonist mediated more dramatic MAP reduction with long‐lasting effect compared with B 1 R 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 B 2 R/B 1 R expression in baroreflex afferent pathway.