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

Aim To study the dominant role of parasympathetic inputs at cellular level of baroreflex afferent pathway and underlying mechanism in neurocontrol of blood pressure regulation. Methods Whole‐cell patch‐clamp and animal study were conducted. Results For the first time, we demonstrated the spontaneous activities from resting membrane potential in myelinated A‐ and Ah‐type baroreceptor neurons (BRNs, the 1st‐order), but not in unmyelinated C‐types, using vagus‐nodose slice of adult female rats. These data were further supported by the notion that the spontaneous synaptic currents could only be seen in the pharmacologically and electrophysiologically defined myelinated A‐ and Ah‐type baroreceptive neurons (the 2nd‐order) of NTS using brainstem slice of adult female rats. The greater frequency and the larger amplitude of the spontaneous excitatory postsynaptic currents (EPSCs) compared with the inhibitory postsynaptic currents (IPSCs) were only observed in Ah‐types. The ratio of EPSCs:IPSCs was estimated at 3:1 and higher. These results confirmed that the afferent‐specific spontaneous activities were generated from baroreflex afferent pathway in female‐specific subpopulation of myelinated Ah‐type BRNs in nodose and baroreceptive neurons in NTS, which provided a novel insight into the dominant role of sex‐specific baroreflex‐evoked parasympathetic drives in retaining a stable and lower blood pressure status in healthy subjects, particularly in females. Conclusion 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

Bis(7-amino-2,4-dimethyl-1,8-naphthyridine)dinitratocadmium(II)

In the title compound, [Cd(NO3)2(C10H11N3)2], two naph­thyridine ring systems are coordinated to the Cd ion through the two N atoms in a bidentate chelating mode, whereas the remaining coordination sites are occupied by two O atoms from two different nitrate groups to complete the octahedral geometry. Inter­moleular N—H⋯O hydrogen bonds link the mol­ecules to form a one-dimensionnal sheet parallel to the ac plane. Weak slipped π–π stacking involving the naphthyridine ring systems stabilizes the structure

Mineralocorticoid receptor antagonists for chronic heart failure: a meta-analysis focusing on the number needed to treat

AimsRecent studies have shown that mineralocorticoid receptor antagonists (MRAs) can decrease mortality in patients with heart failure; however, the application of MRAs in current clinical practice is limited because of adverse effects such as hyperkalemia that occur with treatment. Therefore, this meta-analysis used the number needed to treat (NNT) to assess the efficacy and safety of MRAs in patients with chronic heart failure.MethodsWe meta-analysed randomized controlled trials (RCTs) which contrasted the impacts of MRAs with placebo. As of March 2023, all articles are published in English. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke, and adverse events.ResultsWe incorporated seven studies with a total of 9,056 patients, 4,512 of whom received MRAs and 4,544 of whom received a placebo, with a mean follow-up period of 2.1 years. MACE, all-cause mortality, and cardiovascular mortality were all reduced by MRAs, with corresponding numbers needed to treat for benefit (NNTB) of 37, 28, and 34; as well as no impact on MI or stroke. MRAs increased the incidence of hyperkalemia and gynecomastia, with the corresponding mean number needed to treat for harm (NNTH) of 18 and 52.ConclusionsThis study showed that enabling one patient with HF to avoid MACE required treating 37 patients with MRAs for 2.1 years. MRAs reduce MACE, all-cause mortality, and cardiovascular death; however, they increase the risk of hyperkalemia and gynecomastia

FGF21 ameliorates the neurocontrol of blood pressure in the high fructose-drinking rats

Fibroblast growth factor-21 (FGF21) is closely related to various metabolic and cardiovascular disorders. However, the direct targets and mechanisms linking FGF21 to blood pressure control and hypertension are still elusive. Here we demonstrated a novel regulatory function of FGF21 in the baroreflex afferent pathway (the nucleus tractus solitarii, NTS; nodose ganglion, NG). As the critical co-receptor of FGF21, β-klotho (klb) significantly expressed on the NTS and NG. Furthermore, we evaluated the beneficial effects of chronic intraperitoneal infusion of recombinant human FGF21 (rhFGF21) on the dysregulated systolic blood pressure, cardiac parameters, baroreflex sensitivity (BRS) and hyperinsulinemia in the high fructose-drinking (HFD) rats. The BRS up-regulation is associated with Akt-eNOS-NO signaling activation in the NTS and NG induced by acute intravenous rhFGF21 administration in HFD and control rats. Moreover, the expressions of FGF21 receptors were aberrantly down-regulated in HFD rats. In addition, the up-regulated peroxisome proliferator-activated receptor-γ and -α (PPAR-γ/-α) in the NTS and NG in HFD rats were markedly reversed by chronic rhFGF21 infusion. Our study extends the work of the FGF21 actions on the neurocontrol of blood pressure regulations through baroreflex afferent pathway in HFD rats

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

AbstractObjectiveTo understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness.MethodsDNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening themtDNA 12SrRNA, GJB2andSLC26A4mutations in population–based samples.ResultsA total of 2, 572 Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X–linked, one Y–linked, 28 large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147GJB2induced hearing loss cases, 230 cases with enlarged vestibular aqueduct (EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1, 283 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X–linked families were found transmitting two novel mutations in thePOU3F4gene, while another X–linked family was mapped onto a novel locus, nominated asAUNX1(auditory neuropathy, X–linked locus 1). The only Y–linked family was mapped onto theDFNY1locus (Y–linked locus 1,DFNY1). Eight of the 28 autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2, 567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes:mtDNA 12S rRNA 1555G, GJB2andSLC26A4.The auditory neuropathy cases in our samples were screened forOTOFgene mutations.ConclusionsThese data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalized surveillance and prevention models for hearing loss based on genetic research will provide the opportunity to decrease the prevalence of deafness in the Chinese population