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.

α _{2 -}肾上腺素能受体 (α ₂ -AR) 激动剂右美托咪定增加压力反射敏感性 (BRS)。在当前的研究中，我们检查了孤束核 (NTS) 中腺苷 A1 受体 (A1R) 在这种反应中的潜在作用。简而言之，成年雄性 Sprague-Dawley 大鼠被麻醉并随机接受选择性 A1R 拮抗剂 8-环戊基-1,3-二丙基黄嘌呤（DPCPX；0.1 pmol/1 μl）或生理盐水载体显微注射到右侧 NTS 中。显微注射后 10 分钟，右美托咪定开始以 30 μg/kg 的速度输注 15 分钟，然后以 15 μg·kg ^-1 ·h ^-1的速度输注105 分钟，或以 100 μg/kg 的速度输注 15 分钟，然后在50 μg·kg ^-1 ·h ^-1105 分钟。在开始输注右美托咪定后(T ₀ )、60 分钟 (T ₁ ) 和 120 分钟 (T ₂ )，使用标准去氧肾上腺素方法检查 BRS 。用高效液相色谱法测量血浆和脑干中的腺苷浓度，使用与不使用 α ₂ -AR 拮抗剂阿替美唑预处理 (0.5 mg/kg, ip)。右美托咪定在 30 (T ₀ : 0.55 ± 0.25 vs. T ₁ : 2.45 ± 0.37, T ₂ : 2.26 ± 0.56 ms/mmHg, P <0.05) 和 100 μg/kg (T ₀ : 0.23 vs. 0.64) 时增加 BRS T ₁ : 6.21 ± 1.87, T ₂ : 6.30 ± 2.12 ms/mmHg, P<0.05）。DPCPX 预处理消除了 BRS 对 100-μg/kg 右美托咪定的反应。在 100 μg/kg 时，右美托咪定增加血浆中的腺苷浓度（0.23 ± 0.11 至 0.45 ± 0.07 μg/ml，P <0.05）和脑干（1.46 ± 0.30 至 2.52 ± 0.22 μg/ml，P <0.05）这种作用被阿替美唑预处理所阻断。蛋白质印迹分析显示100-μg/kg 右美托咪定使α ₂ -AR 上调，DPPCX 可以防止这种情况。神经胶质纤维酸性蛋白的双重标记显示NTS 中星形胶质细胞的α ₂ -AR 上调。这些结果表明右美托咪定增强压力反射敏感性，可能是通过增加 NTS 中的腺苷和星形胶质细胞中的α ₂ -AR 表达。