Natriuretic Peptide Improves Impaired Baroreceptor Sensitivity in a Sex-Dependent Manner by Enhancing Baroreflex Afferent Neuroexcitation Under Physiological and Hypertensive Conditions

Metabolic syndrome is a recognized risk factor linked to hypertension, yet the beneficial role of natriuretic peptides (NPs) in this context remains debated. In this study, we established a high-fructose drinking-induced hypertension (HFD-HTN) model in male and female rats. Blood pressure (BP) and baroreceptor sensitivity (BRS) were evaluated, and gene/protein expressions of NP and their receptors were assessed by qRT-PCR and Western blot in the nodose ganglia (NG) and nucleus tractus solitarius (NTS). Our results demonstrated that the elevated systolic BP observed in both sexes of HFD-HTN rats was significantly reduced following NP administration (1.0 μg/g/day, tail vein). Impaired BRS was also ameliorated by NP treatment; the downregulation of NPRA/NPRB and upregulation of NPRC in NG/NTS were reversed. Interestingly, the expression of NR1/GluR2/GluR3 was markedly downregulated in NG but exhibited an inverse pattern in NTS, both of which were normalized by NP treatment. Patch-clamp recordings revealed that NP (100 nM) markedly shortened action potential duration with accelerated repolarization and increased firing frequency of repetitive discharge (FFRD) in C-type NG neurons of both sexes. Notably, the stimulus current required to elicit similar FFRD was significantly lower in female rats/dogs, consistent with their higher BRS. These findings provide new insights into the beneficial role of NPs in neurocontrol of BP regulation and hypertension via modulation of baroreflex afferent function.

baroreflex afferent pathway; glutamate receptor; high fructose‐induced hypertension; natriuretic peptide.