Department of Cardiovascular Medicine, Nephrology and Neurology, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa, Japan.
Department of Infectious, Respiratory and Digestive Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa, Japan.
Hypertens Res. 2018 Oct;41(10):828-838. doi: 10.1038/s41440-018-0088-3. Epub 2018 Aug 17.
Bone marrow-derived cells exert anti-inflammatory actions and can migrate into the brain. However, their role in the development of neurogenic hypertension remains unclear. A hyperactive renin-angiotensin system and inflammation in the brain are mechanisms that contribute to angiotensin II-initiated neurogenic hypertension. We hypothesized that bone marrow-derived cells in the brain attenuate the overactive brain renin-angiotensin system and inflammation, thereby reducing neurogenic hypertension. We cultured plastic-adherent bone marrow-derived cells for 3 weeks. Seven days after initiation of vehicle or angiotensin II infusions, the rats underwent intracerebroventricular administration of either serum-free medium or autologous bone marrow-derived cells (10 cells). After 23 days of infusion, the mean arterial pressure was recorded, and the sympathetic tone was evaluated. Rats infused with angiotensin II demonstrated significant increases in the resting mean arterial pressure and the peak depressor response to ganglionic blockade (vehicle vs. angiotensin II infusion, 119 ± 4 vs. 178 ± 6 mmHg and -34 ± 6 vs. -74 ± 5 mmHg, respectively). Intracerebroventricularly administered bone marrow-derived cells attenuated the angiotensin II-mediated increases in the resting mean arterial pressure and peak depressor response (142 ± 11 and -52 ± 4 mmHg, respectively). The cells also reduced the angiotensin II-induced increases in angiotensin II type 1 receptor and transforming growth factor-β expression in the brain. In conclusion, bone marrow-derived cells in the brain may have a protective role against the development of angiotensin II-induced neurogenic hypertension by modulating angiotensin II type 1 receptor expression and inflammatory processes.
骨髓来源的细胞发挥抗炎作用，并可迁移至脑部。然而，其在神经原性高血压发展中的作用尚不清楚。肾素-血管紧张素系统过度活跃和脑部炎症是导致血管紧张素 II 引发的神经原性高血压的机制。我们假设，脑内的骨髓源性细胞可减弱过度活跃的脑肾素-血管紧张素系统和炎症，从而降低神经原性高血压。我们培养了 3 周的贴壁型骨髓源性细胞。在开始输注载体或血管紧张素 II 7 天后，向大鼠脑室内给予无血清培养基或自体骨髓源性细胞（10 细胞）。输注 23 天后，记录平均动脉压，并评估交感神经张力。输注血管紧张素 II 的大鼠静息平均动脉压和交感神经阻滞的最大降压反应显著增加（载体与血管紧张素 II 输注，119±4与 178±6mmHg 和-34±6与-74±5mmHg）。脑室内给予的骨髓源性细胞减弱了血管紧张素 II 介导的静息平均动脉压和最大降压反应的增加（分别为 142±11 和-52±4mmHg）。这些细胞还降低了血管紧张素 II 诱导的脑内血管紧张素 II 型 1 受体和转化生长因子-β表达的增加。总之，脑内的骨髓源性细胞可能通过调节血管紧张素 II 型 1 受体表达和炎症过程，对血管紧张素 II 诱导的神经原性高血压的发展起到保护作用。
