iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Lisbon, Portugal.
Instituto de Biologia y Genetica Molecular (IBGM), Consejo Superior de Investigaciones Científicas, Universidad de Valladolid, Valladolid, Spain.
Adv Exp Med Biol. 2023;1427:115-125. doi: 10.1007/978-3-031-32371-3_13.
Endothelial dysfunction is an essential intermediary for development of cardiovascular diseases associated with diabetes and hypertension (HT). The carotid body (CB) dysfunction contributes to dysmetabolic states, and the resection of carotid sinus nerve (CSN) prevents and reverts dysmetabolism and HT. Herein, we investigated if CSN denervation ameliorates systemic endothelial dysfunction in an animal model of type 2 diabetes mellitus (T2DM).We used Wistar male rats submitted to HFHSu diet during 25 weeks and the correspondent age-matched controls fed with a standard diet. CSN resection was performed in half of the groups after 14 weeks of diet. In vivo insulin sensitivity, glucose tolerance and blood pressure, ex vivo aortic artery contraction and relaxation and nitric oxide (NO) levels in plasma and aorta, aorta nitric oxide synthase (NOS) isoforms, and PGF2αR levels were evaluated.We demonstrated that, alongside to dysmetabolism and HT reversion, CSN resection restores endothelial function in the aorta and decreases the NO levels in plasma and aorta at the same time that restores normal levels of iNOS in aorta without changing eNOS or PGF2αR levels.These results suggest that the modulation of CB activity can be important for the treatment of HT and endothelial dysfunction related with T2DM.
内皮功能障碍是与糖尿病和高血压（HT）相关的心血管疾病发展的重要中介。颈动脉体（CB）功能障碍导致代谢紊乱，而颈动脉窦神经（CSN）切除术可预防和逆转代谢紊乱和 HT。在此，我们研究了 CSN 去神经支配是否能改善 2 型糖尿病（T2DM）动物模型中的全身内皮功能障碍。我们使用 Wistar 雄性大鼠进行了 25 周的 HFHSu 饮食，并对相应的年龄匹配的对照组进行了标准饮食喂养。在饮食 14 周后，一半的组进行了 CSN 切除术。在体内评估了胰岛素敏感性、葡萄糖耐量和血压、离体主动脉收缩和舒张以及血浆和主动脉中的一氧化氮（NO）水平、主动脉一氧化氮合酶（NOS）同工型和 PGF2αR 水平。我们证明，除了代谢紊乱和 HT 逆转外，CSN 切除还可恢复主动脉内皮功能，并降低同时恢复正常水平的 iNOS 在主动脉而不改变 eNOS 或 PGF2αR 水平的血浆和主动脉中的 NO 水平。这些结果表明，CB 活性的调节对于治疗与 T2DM 相关的 HT 和内皮功能障碍可能很重要。
