Adenosine and nitric oxide act on the fine-tuning regulation of neural cardiovascular control in the nucleus tractus solitarius (NTS). Although the interaction between adenosine and NO is well known in the periphery, the mechanisms by which adenosine interferes in the dynamics of nitrergic neurotransmission, related to neural control of circulation, are not completely understood and might be relevant for individuals predisposed to hypertension. In this study we evaluate the interaction between adenosinergic and nitrergic systems in cell culture from the dorsomedial medulla oblongata of Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). Using quantification of nitrite levels, RT-PCR analysis and RNA interference we demonstrate that adenosine A1 (A1R) and A2a receptor (A2aR) agonists induce a concentration-dependent decrease and increase of nitrite and nNOS mRNA levels in cultured cells from WKY and SHR, respectively. These effects in nitrite levels are attenuated by the administration of A1R and A2aR selective antagonists, CPT and ZM 241385. Furthermore, knockdown of A1R and A2aR show an increase and decrease of nNOS mRNA levels, respectively. Pretreatment with the nonselective inhibitor of NOS, L-NAME, abolishes nitrite-increased levels triggered by CGS 21680 in WKY and SHR cells. Finally, it is shown that the cAMP-PKA pathway is involved in A1R and A2aR-mediated decrease and increase in nitrite levels in SHR and WKY cells. Our results highlight the influence of adenosine on nitric oxide levels in cultured cells from dorsal medulla oblongata of neonate WKY and SHR rats. In part, the modulatory profile is different in the SHR strain.

中文翻译：

---

腺苷 A1 和 A2a 受体调节延髓背内侧细胞培养物中的氮能系统

腺苷和一氧化氮作用于孤束核 (NTS) 神经心血管控制的微调调节。虽然腺苷和 NO 之间的相互作用在外周众所周知，但腺苷干扰与循环神经控制相关的氮能神经传递动力学的机制尚不完全清楚，可能与易患高血压的个体相关。在这项研究中，我们评估了 Wistar 京都 (WKY) 和自发性高血压大鼠 (SHR) 的背内侧延髓细胞培养物中腺苷能和氮能系统之间的相互作用。使用亚硝酸盐水平的量化，RT-PCR 分析和 RNA 干扰我们证明腺苷 A1 (A1R) 和 A2a 受体 (A2aR) 激动剂分别诱导 WKY 和 SHR 培养细胞中亚硝酸盐和 nNOS mRNA 水平的浓度依赖性降低和增加。这些对亚硝酸盐水平的影响通过施用 A1R 和 A2aR 选择性拮抗剂 CPT 和 ZM 241385 减弱。此外，A1R 和 A2aR 的敲低分别显示 nNOS mRNA 水平的增加和减少。用非选择性 NOS 抑制剂 L-NAME 进行预处理可消除 WKY 和 SHR 细胞中由 CGS 21680 引发的亚硝酸盐水平升高。最后，显示 cAMP-PKA 通路参与 SHR 和 WKY 细胞中 A1R 和 A2aR 介导的亚硝酸盐水平的降低和增加。我们的研究结果强调了腺苷对新生 WKY 和 SHR 大鼠延髓背侧培养细胞中一氧化氮水平的影响。部分地，SHR 菌株的调节曲线不同。