T he sex difference in blood pressure (BP) has long been recognized between premenopausal women and agedmatched men.1 Women are protected from most cardiovascular events compared with age-matched men before menopause, and postmenopausal women are at increased risk of cardiovascular complications compared with premenopausal women. 2 The pathophysiological mechanisms have been extensively explored, and increasing evidences have shown that the female hormone is one of the major mechanisms contributing to the above phenomena.3 Several studies have demonstrated the importance of the interaction between sex hormones and the renin-angiotensin system in regulating cardiovascular function and BP. 4,5 Angiotensin-II (Ang-II) is a key player in the development of hypertension. Ang-II type-1 (AT 1 R) and type-2 (AT 2 R) receptors play opposite roles in BP regulation, 6,7 with AT 2 R exerting a cardioprotective action in essential hypertension. 8 Early study demonstrates that AT 2 R provides a major clue for solving the mystery of sex differences in AT 2 R-mediated vasodilation 9 and hypertension. 10 However, the majority of researches on hypertension to date has been conducted in male animals and focused largely on the target organs, such as the heart, blood vessels, and kidney. The sex differences in neurocontrol of circulation at baroreflex level have almost been neglected although AT 1 R or AT 2 R has been identified in nodose ganglia (NG) or nucleus of tractus solitary (NTS). 11,12 Recent literatures have shown that adult female rats express Abstract-This study aims to understand the special expression patterns of angiotensin-II receptor (AT 1 R and AT 2 R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT 1 R and AT 2 R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT 2 R expression were also tested. The data showed that AT 2 R, rather than AT 1 R, expression was higher in female than age-matched male rats. Moreover, AT 2 R was downregulated in ovariectomized rats, which was restored by the administration of 17β-estradiol. Single-cell real time-polymerase chain reaction data indicated that AT 2 R was uniquely expressed in Ah-type BRNs. Functional study showed that long-term administration of 17β-estradiol significantly alleviated the blood pressure increase in ovariectomized rats. Electrophysiological recordings showed that angiotensin-II treatment increased the neuroexcitability more in Ah-than C-type BRNs, whereas no such effect was observed in A-types. In addition, angiotensin-II treatment prolonged action potential duration, which was not further changed...

BackgroundKetamine enhances autonomic activity, and unmyelinated C-type baroreceptor afferents are more susceptible to be blocked by ketamine than myelinated A-types. However, the presynaptic transmission block in low-threshold and sex-specific myelinated Ah-type baroreceptor neurons (BRNs) is not elucidated.MethodsAction potentials (APs) and excitatory post-synaptic currents (EPSCs) were investigated in BRNs/barosensitive neurons identified by conduction velocity (CV), capsaicin-conjugated with Iberiotoxin-sensitivity and fluorescent dye using intact nodose slice and brainstem slice in adult female rats. The expression of mRNA and targeted protein for NMDAR1 was also evaluated.ResultsKetamine time-dependently blocked afferent CV in Ah-types in nodose slice with significant changes in AP discharge. The concentration-dependent inhibition of ketamine on AP discharge profiles were also assessed and observed using isolated Ah-type BRNs with dramatic reduction in neuroexcitability. In brainstem slice, the 2nd-order capsaicin-resistant EPSCs were identified and ∼50% of them were blocked by ketamine concentration-dependently with IC50 estimated at 84.4 μM compared with the rest (708.2 μM). Interestingly, the peak, decay time constant, and area under curve of EPSCs were significantly enhanced by 100 nM iberiotoxin in ketamine-more sensitive myelinated NTS neurons (most likely Ah-types), rather than ketamine-less sensitive ones (A-types).ConclusionsThese data have demonstrated, for the first time, that low-threshold and sex-specific myelinated Ah-type BRNs in nodose and Ah-type barosensitive neurons in NTS are more susceptible to ketamine and may play crucial roles in not only mean blood pressure regulation but also buffering dynamic changes in pressure, as well as the ketamine-mediated cardiovascular dysfunction through sexual-dimorphic baroreflex afferent pathway.

. (2015). KCa1.1 β4-subunits are not responsible for iberiotoxin-resistance in baroreceptor neurons in adult male rats.