Adenosine A1 receptors of the medullary solitary tract arbitrate the nicotine counteraction of neuroinflammation and cardiovascular dysfunction in septic rats

Figures

• 

  Figure 1. The dose-dependent increase in time-course (panels A–C) and cumulative changes (areas under the curves, AUCs, panels (B–D)) in mean arterial pressure (MAP) and heart rate (HR) caused by i.v. nicotine (25 or 100 μg/kg) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 7–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “sham/saline”, bP < 0.05 vs. “CLP/saline”.

• 

  Figure 2. The dose-dependent increase in time-course (panels A–C) and cumulative changes (areas under the curves, AUCs, panels B–D) in time-domain indices of HRV (SDNN, the standard deviation of NN intervals, and rMSSD, the square root of the mean squared differences of successive NN intervals, as measures of overall HRV and parasympathetic activity, respectively) evoked by i.v. nicotine (25, 100 μg/kg) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 6–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “sham/saline”, bP < 0.05 vs. “CLP/saline”.

• 

  Figure 3. The dose-dependent increase in time-course (panels A–C) and cumulative changes (areas under the curves, AUCs, panels B–D) in frequency-domain indices of HRV (total power and LF/HF ratio, the ratio of low frequency range to high frequency range as measures of overall HRV and sympathovagal balance, respectively) induced by i.v. nicotine (25, 100 μg/kg) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 6–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “sham/saline”, bP < 0.05 vs. “CLP/saline”.

• 

  Figure 4. Effects of central adenosine A1 receptor activation (CPA) or blockade (DPCPX) on the nicotine-evoked changes in time-course (panels A–C) and cumulative (areas under the curves, AUCs, panels B–D) values of mean arterial pressure (MAP) and heart rate (HR) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 6–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “CLP/saline”, bP < 0.05 vs. “CLP/NIC”.

• 

  Figure 5. Effects of central adenosine A1 receptor activation (CPA) or blockade (DPCPX) on the nicotine-evoked increase in time-course (panels A–C) and cumulative changes (areas under the curves, AUCs, panels B–D) in time-domain indices of HRV (SDNN, the standard deviation of NN intervals, and rMSSD, the square root of the mean squared differences of successive NN intervals, as measures of overall HRV and parasympathetic activity, respectively) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 6–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “CLP/saline”, bP < 0.05 vs. “CLP/NIC”, cP < 0.05 vs. “CLP/CPA”.

• 

  Figure 6. Effects of central adenosine A1 receptor activation (CPA) or blockade (DPCPX) on the nicotine-evoked increase in time-course (panels A–C) and cumulative changes (areas under the curves, AUCs, panels B–D) in frequency-domain indices of HRV (total power and LF/HF ratio, ratio of low frequency range to high frequency range, as measures of overall HRV and sympathovagal balance, respectively) in septic (cecal ligation and puncture, CLP) male rats. Values are means ± SEM of 6–8 observations. The one-way (panels A–C) and repeated measures ANOVA (panels B–D) followed by the Tukey’s post hoc test were employed to test for statistical significance. aP < 0.05 vs. “CLP/saline”, bP < 0.05 vs. “CLP/NIC”, cP < 0.05 vs. “CLP/CPA”.

• 

  Figure 7. Effects of i.v. nicotine and/or i.c. CPA (A1R agonist) or DPCPX (A1R antagonist) on NFκB expression in hearts and brainstem areas of NTS (nucleus tractus solitarius) and RVLM (rostral ventrolateral medulla) of septic (cecal ligated and puncture, CLP) rats. Values are means ± SEM of 4–5 observations. The one-way ANOVA followed by the Tukey’s post hoc test was employed to test for statistical significance. aP < 0.05 vs. “sham/saline”, bP < 0.05 vs. “CLP/saline”, cP < 0.05 vs. “CLP/NIC”.

• 

  Figure 8. Effects of i.v. nicotine and/or i.c. CPA (A1R agonist) or DPCPX (A1R antagonist) on A1AR expression in hearts and brainstem areas of NTS (nucleus tractus solitarius) and RVLM (rostral ventrolateral medulla) of septic (cecal ligated and puncture, CLP) rats. Values are means ± SEM of 4–5 observations. The one-way ANOVA followed by the Tukey’s post hoc test was employed to test for statistical significance. aP < 0.05 vs. “sham/saline”, cP < 0.05 vs. “CLP/NIC”.

• 

  Figure 9. Diagrammatic representation of the timeline of surgical procedures and drug regimens.