Blockade of adenosine A1 receptor in nucleus tractus solitarius attenuates baroreflex sensitivity response to dexmedetomidine in rats

The α₂-adrenergic receptor (α₂-AR) agonist dexmedetomidine increases baroreflex sensitivity (BRS). In the current study, we examined the potential role of adenosine A1 receptor (A1R) within the nucleus tractus solitaries (NTS) in such a response. Briefly, adult male Sprague-Dawley rats were anesthetized and randomly received microinjection of selective A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 pmol/1 μl) or saline vehicle into the right NTS. Ten min after the microinjection, dexmedetomidine infusion started at a rate of 30 μg/kg over 15 min followed by infusion at 15 μg·kg^-1·h^-1 for 105 min, or 100 μg/kg over 15 min followed by infusion at 50 μg·kg^-1·h^-1 for 105 min. BRS was examined using a standard phenylephrine method prior to infusion (T₀), 60 min (T₁) and 120 min (T₂) after dexmedetomidine infusion started. Adenosine concentration in plasma and brainstem was measured with high-performance liquid chromatography with vs. without α₂-AR antagonist atipamezole pretreatment (0.5 mg/kg, i.p.). Dexmedetomidine increased BRS at both 30 (T₀: 0.55 ± 0.25 vs. T₁: 2.45 ± 0.37, T₂: 2.26 ± 0.56 ms/mmHg, P < 0.05) and 100 μg/kg (T₀: 0.63 ± 0.24 vs. T₁: 6.21 ± 1.87, T₂: 6.30 ± 2.12 ms/mmHg, P < 0.05). DPCPX pretreatment obliterated BRS response to 100-μg/kg dexmedetomidine. At 100 μg/kg, dexmedetomidine increased adenosine concentration in plasma (0.23 ± 0.11 to 0.45 ± 0.07 μg/ml, P < 0.05) and brainstem (1.46 ± 0.30 to 2.52 ± 0.22 μg/ml, P < 0.05); such effect was blocked by atipamezole pretreatment. Western blot analysis showed α₂-AR up-regulation by 100-μg/kg dexmedetomidine, which can be prevented by DPCPX. Double-labeling with glial fibrillary acidic protein showed α₂-AR up-regulation in astrocytes in the NTS. These results suggest that dexmedetomidine enhances baroreflex sensitivity, possibly by increasing adenosine in NTS and α₂-AR expression in astrocytes.