Subdiaphragmatic vagal nerve stimulation attenuates the development of hypertension and alters nucleus of the solitary tract transcriptional networks in the spontaneously hypertensive rat

Figures

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  Figure 1.. Effect of chronic intermittent stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on blood pressure of spontaneously hypertensive rats. Changes (Δ) in systolic blood pressure (SBP; left), diastolic blood pressure (DBP; middle), and mean blood pressure (MBP; right) from baseline (week 0) are shown as means ± SE. Blood pressure values represent averages of 24-h recordings taken once per week, averaged within treatment groups and per week. The light green shaded areas on the x-axis represent the chronic stimulation timeline. n = 5/group. Green, sdVNS; purple, sham. Two-way ANOVA was used for analysis. *P < 0.05, within-group comparison with baseline; #P < 0.05 and ##P < 0.01, effect of treatment; &P < 0.05, effect of treatment × time.

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  Figure 2.. Effect of chronic intermittent stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on blood pressure during 12-h light and dark cycles. Changes (Δ) in systolic blood pressure (SBP; left), diastolic blood pressure (DBP; middle), and mean blood pressure (MBP; right) from baseline (week 0) are shown as means ± SE during light (top) and dark (bottom) cycles. Blood pressure values represent averages of 12-h recordings taken during light and dark cycle once every week, averaged within treatment groups and per week. The light green shaded areas on the x-axis represent the chronic stimulation timeline. n = 5/group. Green, sdVNS; purple, sham. Two-way ANOVA was used for analysis. *P < 0.05, within-group comparison with baseline; #P < 0.05, comparison between groups within the same time point; ^^^P < 0.001, effect of treatment; &P < 0.05, effect of treatment × time.

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  Figure 3.. Effect of chronic intermittent stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on immune markers in the spontaneously hypertensive rat. No differences in the measured inflammatory markers in the serum (A) or proximal colon (B) were detected between the sham and sdVNS groups at endpoint. Similarly, there were no changes in the relative expression levels of select immune-related genes in the proximal colon of spontaneously hypertensive rats following sdVNS (C). Finally, no difference in circulating (serum) levels of catecholamines (D) or circulating (serum) and colonic levels of corticosterone (E) were observed between sham and sdVNS groups at endpoint. Data are presented as scatterplots. Values are represented as means; n = 4 or 5/group. Significance was tested using a Student’s t test.

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  Figure 4.. Effect of chronic intermittent stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on the composition and abundance of gut bacteria in the spontaneously hypertensive rat. No differences in the major bacterial phyla (A), Shannon diversity (B), or Firmicutes-to-Bacteriodetes ratio (F/B ratio; C) were observed between the treatment groups (purple: sham; green: sdVNS). The cladogram (D) and bar graph (E) represent the enrichment in Defluviitaleaceae gut bacterium in the sham group (purple-shaded region) compared with the sdVNS group. In D, yellow spheres represent no taxonomic differences between the two groups on average. In E, purple bars represent individual relative abundances of Defluviitaleaceae gut bacterium detected in three of five samples in the sham group. Data are presented as scatterplots. Values are represented as means in A–C; n = 5/group. Significance was tested using a Student’s t test in A–C.

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  Figure 5.. Effect of chronic intermittent stimulation of the ventral subdiaphragmatic vagal nerve branch (sdVNS) on the nucleus of the solitary tract (NTS) transcriptome in the spontaneously hypertensive rat. A: overview of transcriptional responses in the NTS following sdVNS. DEGs, differentially expressed genes in the NTS (P < 0.05). The arrow indicates the overall trend in network response in the NTS. B: the network related to microglia was increased overall (transcripts shown are P < 0.05). C: networks related to several neurotransmitters and peptides were increased overall (transcripts shown are P < 0.05). D: the gene network related to the vagal nerve was increased overall (transcripts shown are P < 0.05). Blue indicates transcripts with a negative fold change relative to control, whereas red indicates a positive fold change relative to control. All networks depicted are significantly enriched in the NTS. All network data are detailed in the Supplemental Data. Gene names and abbreviations are defined in the Supplemental Data. i, inside of the cell; o, outside of the cell. n = 5/group. VNS, vagal nerve stimulation. Graphical abstract created with BioRender and published with permission.