The Cholinergic Amelioration of Sepsis-Induced Baroreflex Dysfunction and Brainstem Inflammation Is Negated by Central Adenosine A3 Receptors

Figures

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  Figure 1. Effect of i.v. nicotine (NIC, 25−100 μg/kg) on increases and decreases in MAP (A,C) and associated reflex chronotropic responses (B,D) evoked by phenylephrine (1−16 μg/kg) and sodium nitroprusside (1−16 μg/kg), respectively, in septic rats. Values are means ± SEM of 7−8 observations. a p < 0.05 vs. “sham/saline” values, b p < 0.05 vs. “CLP/saline” values.

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  Figure 2. Effect of i.v. nicotine (NIC, 25−100 μg/kg) on baroreflex curves generated by phenylephrine (PE, 1−16 μg/kg) or sodium nitroprusside (SNP, 1−16 μg/kg) (A,B) and slopes of regression lines (C,D) in septic rats. Values are means ± SEM of 7−8 observations. a p < 0.05 vs. “sham/saline” values, b p < 0.05 vs. “CLP/saline” values.

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  Figure 3. Effect of i.c. IB-MECA (A3AR agonist, 4 µg/rat) or VUF5574 (A3AR antagonist, 2 µg/rat) in the absence and presence of nicotine (NIC, 100 μg/kg) on baroreflex curves generated by phenylephrine (PE, 1−16 μg/kg) (A,B) and slopes of regression lines (C) in septic rats. Values are means ± SEM of 7−8 observations. a p < 0.05 vs. “sham/saline” values, b p < 0.05 vs. “CLP/saline” values.

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  Figure 4. Effect of i.c. PD 98059 (MAPK-ERK inhibitor), SP 600125 (MAPK-JNK inhibitor), wortmannin (WORT, PI3K inhibitor), or infliximab (INFLIX, TNFα inhibitor) on baroreflex curves generated by phenylephrine (PE, 1−16 μg/kg, (A–D)) and slopes of the regression lines (E) in the presence of IB-MECA/nicotine-treated septic male rats. Values are means ± SEM of 7−8 observations. a p < 0.05 vs. “CLP/IB-MECA/NIC” values.

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  Figure 5. Effect of i.c. IB-MECA (A3AR agonist) alone and in the presence of PD 98059 (MAPK-ERK inhibitor), SP 600125 (MAPK-JNK inhibitor), wortmannin (WORT, PI3K inhibitor), or infliximab (INFLIX, TNFα inhibitor) on the nicotine-evoked downregulation of NFκB expression in septic (CLP) brainstem areas of NTS (A). Representative images are shown in panel B. a p < 0.05 vs. “sham/saline”, b p < 0.05 vs. “CLP/saline”, c p < 0.05 vs. “CLP/NIC”. d p < 0.05 vs. “CLP/IB-MECA/NIC”.

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  Figure 6. Effect of i.c. IB-MECA (A3AR agonist) alone and in the presence of PD 98059 (MAPK-ERK inhibitor), SP 600125 (MAPK-JNK inhibitor), wortmannin (WORT, PI3K inhibitor), or infliximab (INFLIX, TNFα inhibitor) on the nicotine-evoked downregulation of elevated NOX2 expression in septic (CLP) brainstem areas of NTS (A). Representative images are shown in panel (B). a p < 0.05 vs. “sham/saline”, b p < 0.05 vs. “CLP/saline”, c p < 0.05 vs. “CLP/NIC”.

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  Figure 7. The timeline of surgical procedures and drug regimens employed in experiments.