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.