Department of Physiology and Pathology, Dentistry School, São Paulo State University (UNESP), Araraquara, SP, Brazil.
School of Medicine, Pharmacy and Biomedicine, Pontifical Catholic University of Goias, Goiania, GO, Brazil.
Hypertens Res. 2020 Nov;43(11):1192-1203. doi: 10.1038/s41440-020-0474-5. Epub 2020 May 27.
Intracerebroventricular (icv) injection of hydrogen peroxide (HO) or the increase of endogenous HO centrally produced by catalase inhibition with 3-amino-1,2,4-triazole (ATZ) injected icv reduces the pressor responses to central angiotensin II (ANG II) in normotensive rats. In the present study, we investigated the changes in the arterial pressure and in the pressor responses to ANG II icv in spontaneously hypertensive rats (SHRs) and 2-kidney, 1-clip (2K1C) hypertensive rats treated with HO injected icv or ATZ injected icv or intravenously (iv). Adult male SHRs or Holtzman rats (n = 5-10/group) with stainless steel cannulas implanted in the lateral ventricle were used. In freely moving rats, HO (5 μmol/1 μl) or ATZ (5 nmol/1 μl) icv reduced the pressor responses to ANG II (50 ng/1 µl) icv in SHRs (11 ± 3 and 17 ± 4 mmHg, respectively, vs. 35 ± 6 mmHg) and 2K1C hypertensive rats (3 ± 1 and 16 ± 3 mmHg, respectively, vs. 26 ± 2 mmHg). ATZ (3.6 mmol/kg of body weight) iv alone or combined with HO icv also reduced icv ANG II-induced pressor response in SHRs and 2K1C hypertensive rats. Baseline arterial pressure was also reduced (-10 to -15 mmHg) in 2K1C hypertensive rats treated with HO icv and ATZ iv alone or combined and in SHRs treated with HO icv alone or combined with ATZ iv. The results suggest that exogenous or endogenous HO acting centrally produces anti-hypertensive effects impairing central pressor mechanisms activated by ANG II in SHRs or 2K1C hypertensive rats.
脑室内（icv）注射过氧化氢（HO）或通过 3-氨基-1,2,4-三唑（ATZ）抑制脑内过氧化氢酶增加内源性 HO，可降低正常血压大鼠对中枢血管紧张素 II（ANG II）的升压反应。在本研究中，我们研究了脑室内注射 HO 或 ATZ 或静脉注射（iv）对自发性高血压大鼠（SHR）和 2 肾 1 夹（2K1C）高血压大鼠的动脉压和对 ANG II icv 的升压反应的变化。使用植入侧脑室不锈钢套管的成年雄性 SHR 或霍尔茨曼大鼠（n=5-10/组）。在自由活动的大鼠中，HO（5μmol/1μl）或 ATZ（5nmol/1μl）icv 降低了 SHR（分别为 11±3 和 17±4mmHg，vs. 35±6mmHg）和 2K1C 高血压大鼠（分别为 3±1 和 16±3mmHg，vs. 26±2mmHg）对 ANG II icv（50ng/1µl）的升压反应。ATZ（3.6mmol/kg 体重）iv 单独或与 HO icv 联合使用也降低了 SHR 和 2K1C 高血压大鼠 icv ANG II 引起的升压反应。单独脑室内注射 HO 和 ATZ iv 联合或单独脑室内注射 HO 和 ATZ iv 联合也降低了 2K1C 高血压大鼠的基础动脉压（-10 至-15mmHg）。结果表明，中枢作用的外源性或内源性 HO 产生抗高血压作用，损害了 SHR 或 2K1C 高血压大鼠中由 ANG II 激活的中枢加压机制。
