Chronic administration of catalase inhibitor attenuates hypertension in renovascular hypertensive rats

• Published in: Life sciences (1973) Vol. 319; p. 121538
• Main Authors: Lauar, Mariana R., Colombari, Débora S.A., De Paula, Patrícia M., Colombari, Eduardo, Andrade, Carina A.F., De Luca Jr, Laurival A., Menani, José V.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-04-2023
• Subjects: Angiotensin II; Angiotensin II - pharmacology; Animals; Autonomic modulation; Blood Pressure; Catalase; Catalase inhibitor; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Hypertension; Hypertension - drug therapy; Hypertension, Renovascular - drug therapy; Kidney Diseases; Male; Neuro-inflammation; Rats; Rats, Sprague-Dawley; RNA, Messenger; Sympathetic activity; Sympathetic activity; O2; SAP; Hydrogen peroxide; RAS; ATZ; CNS; PVN; HR; H2O2; Catalase inhibitor; ANG II; MSA; 2K1C; SHR; Angiotensin II; icv; Hypertension; Neuro-inflammation; SOD; iv; Autonomic modulation; ROS; NAD(P)H; MAP; PAP
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121538

Reactive oxygen species like hydrogen peroxide (H2O2) are produced endogenously and may participate in intra- and extracellular signaling, including modulation of angiotensin II responses. In the present study, we investigated the effects of chronic subcutaneous (sc) administration of the catalase inhibitor 3-amino-1,2,4-triazole (ATZ) on arterial pressure, autonomic modulation of arterial pressure, hypothalamic expression of AT1 receptors and neuroinflammatory markers and fluid balance in 2-kidney, 1clip (2K1C) renovascular hypertensive rats.
Male Holtzman rats with a clip occluding partially the left renal artery and chronic sc injections of ATZ were used.
Subcutaneous injections of ATZ (600 mg/kg of body weight/day) for 9 days in 2K1C rats reduced arterial pressure (137 ± 8, vs. saline: 182 ± 8 mmHg). ATZ also reduced the sympathetic modulation and enhanced the parasympathetic modulation of pulse interval, reducing the sympatho-vagal balance. Additionally, ATZ reduced mRNA expression for interleukins 6 and IL-1β, tumor necrosis factor-α, AT1 receptor (0.77 ± 0.06, vs. saline: 1.47 ± 0.26 fold change), NOX 2 (0.85 ± 0.13, vs. saline: 1.75 ± 0.15 fold change) and the marker of microglial activation, CD 11 (0.47 ± 0.07, vs. saline, 1.34 ± 0.15 fold change) in the hypothalamus of 2K1C rats. Daily water and food intake and renal excretion were only slightly modified by ATZ.
The results suggest that the increase of endogenous H2O2 availability with chronic treatment with ATZ had an anti-hypertensive effect in 2K1C hypertensive rats. This effect depends on decreased activity of sympathetic pressor mechanisms and mRNA expression of AT1 receptors and neuroinflammatory markers possibly due to reduced angiotensin II action.
Representative schematic of the main finds of this study showing the effects of the injection of ATZ decreasing proinflammatory cytokines, AT1 receptor expression, and microglia activation in the hypothalamus of hypertensive rats leading to a decrease in cardiac and vasomotor sympathetic modulation that contribute to the decrease in hypertension in the 2K1C hypertensive animals. [Display omitted]