Autonomic Neuroscience ( IF 3.2 ) Pub Date : 2023-07-09 , DOI: 10.1016/j.autneu.2023.103107 Roberto Braz Pontes 1 , Débora S A Colombari 1 , Patrícia M De Paula 1 , Eduardo Colombari 1 , Carina A F Andrade 1 , Laurival A De Luca 1 , José V Menani 1
Previous studies from our laboratory have shown that the pressor response to intracerebroventricular (icv) administered ANG II in normotensive rats or spontaneously hypertensive rats (SHRs) is attenuated by increased central H2O2 concentration, produced either by direct H2O2 icv injection or by increased endogenous H2O2 centrally in response to local catalase inhibition with 3-amino-1,2,4-triazole (ATZ). In the present study, we evaluated the effects of ATZ administered peripherally on arterial pressure and sympathetic and angiotensinergic activity in SHRs. Male SHRs weighing 280–330 g were used. Mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious freely moving SHRs. Acute intravenous injection of ATZ (300 mg/kg of body weight) did not modify MAP and HR during the next 4 h, however, the treatment with ATZ (300 mg/kg of body weight twice per day) for 3 days reduced MAP (144 ± 6, vs. saline, 183 ± 13 mmHg), without changing HR. Intravenous hexamethonium (ganglionic blocker) produced a smaller decrease in MAP 4 h after ATZ (−25 ± 3, vs saline −38 ± 4 mmHg). Losartan (angiotensinergic AT1 receptor blocker) produced a significant depressor response 4 h after ATZ (−22 ± 4, vs. saline: −2 ± 4 mmHg) and in 3-day ATZ treated SHRs (−25 ± 5, vs. saline: −9 ± 4 mmHg). The results suggest that the treatment with ATZ reduces sympathetic activity in SHRs and simultaneously increases angiotensinergic activity.
中文翻译:
3-氨基-1,2,4-三唑治疗自发性高血压大鼠的交感神经和血管紧张素活性
我们实验室之前的研究表明,正常血压大鼠或自发性高血压大鼠 (SHR) 对侧脑室 (icv) 给予 ANG II 的升压反应会因直接 H 2 O 2 icv 注射产生的中心 H 2 O 2浓度增加而减弱或通过增加内源性 H 2 O 2来响应 3-氨基-1,2,4-三唑 (ATZ) 的局部过氧化氢酶抑制。在本研究中,我们评估了外周给药 ATZ 对 SHR 中动脉压以及交感神经和血管紧张素能活性的影响。使用体重为 280-330 克的雄性 SHR。在有意识、自由活动的 SHR 中记录平均动脉压(MAP) 和心率 (HR)。急性静脉注射ATZ(300 mg/kg 体重)在接下来的 4 小时内没有改变 MAP 和 HR,然而,用 ATZ(300 mg/kg 体重每天两次)治疗 3 天降低了 MAP( 144 ± 6,对比生理盐水,183 ± 13 mmHg),不改变 HR。ATZ 后 4 小时静脉注射六甲铵(神经节阻滞剂)可使 MAP 产生较小的下降(−25 ± 3,与生理盐水 -38 ± 4 mmHg)。氯沙坦(血管紧张素 AT 1受体阻滞剂)在 ATZ 后 4 小时(-22 ± 4,对比生理盐水:-2 ± 4 mmHg)和 3 天 ATZ 治疗的 SHR(-25 ± 5,对比生理盐水)产生显着的抑制反应:−9±4毫米汞柱)。结果表明,ATZ 治疗可降低 SHR 的交感神经活性,同时增加血管紧张素能活性。