Activation of the Sympathetic Nervous System Promotes Blood Pressure Salt-Sensitivity in C57BL6/J Mice

Figure 1.. Cardiovascular parameters and activity in male C57BL6/J mice. A, Systolic blood pressure, (B) diastolic blood pressure, (C) heart rate and (D) locomotor activity recorded by radio-telemetry devices implanted into the carotid artery of male C57BL6/J mice (n=7).Data were acquired every 20 min over a longitudinal protocol (Figure S1) incorporating control diet (0.3% Na) baseline; 21 d of high salt (3% Na) and a washout phase when mice were returned to 0.3% Na diet. Data are presented as 5-hour rolling averages (group mean solid line) ±SD (dashed lines).

Figure 2.. Male C57BL6/J mice (n=7; 10–12 wk old) were individually housed in metabolism cages for measurement of food/water intake and urine/fecal output over 7 d of the control diet (0.3% Na; open circles), followed by 7 d of high-salt diet (3% Na; red squares). A, Cumulative sodium balance and (B) cumulative water balance were calculated for each 7-d period, presented as individual data points with median±interquartile range, and analyzed nonparametrically by Kruskal-Wallis test. C, Hematocrit, measured from arterial blood in male C57BL6/J mice fed either control diet (open circles; n=14) or high-salt diet (red squares) for 3 d (n=8) and 7 d (n=7). Individual data points, with mean±SD, were analyzed by 1-way ANOVA and groups were not significantly different. D, sodium excretion; (E) chloride excretion and (F) urine flow rate during the day (D: inactive phase 7 am–7 pm) and night (N: active phase 7 pm–7 am). Individual data points and group mean±SD are shown and analyzed by repeated-measures 2-way ANOVA for main effects of time of day and diet. P values for planned comparisons are given, made Holm-Sidak testing.

Figure 3.. The acute pressure natriuresis relationship in anesthetized male C57BL6/J mice fed either control diet (0.3% Na, open circles; n=9) or high sodium (3% Na; red squares; n=7) for 3 days. Blood pressure (BP) was acutely raised over baseline by sequential ligation of the mesenteric and coeliac arteries (first pressure ramp) and the distal aorta (second pressure ramp). And urine collected via bladder cannula. A, The BP profile over the time course was not different between groups. B, Sodium excretion, (C) urine flow rate, (D) renal blood flow, (F) glomerular filtration rate (GFR). Data are group mean±SD and statistical analysis was by 2-way ANOVA. P values for planned comparisons between groups are given, made Holm-Sidak testing.

Figure 4.. The acute depressor effect of ganglionic blockade was used to index sympathetic nervous system activity in male C57BL6/J mice (n=7) fed control diet (0.3% Na, open circles) and then high-salt diet (3% Na; red squares) as indicated in the protocol (Figure S1). A, resting systolic blood pressure (SBP). B, The maximum drop in SBP induced by hexamethonium (Δhexamethonium). C, the time taken for SBP to return to preinjection baseline. D, Area over the curve. Individual mouse data are shown with group mean±SD. Analysis was by repeated-measures 1-way ANOVA with P values shown for post-test comparisons to the control. In a separate group of mice (n=7), measurements of (E) urinary excretion of norepinephrine and (F) epinephrine during the day (D: inactive phase 7 am–7 pm) and night (N: active phase 7 pm–7 am) were made first on control diet (0.3% Na, open circles) and then after 7-d of high-salt diet (3% Na; red squares). Individual mice and group means±SD are shown. Analysis was by repeated-measures 2-way ANOVA, with main effects of diet and time of day. Planned post-test comparisons were performed by Holm-Sidak with P values indicated.