Zhang Yi, Jang Ryan, Mori Trevor A, Croft Kevin D, Schyvens Christopher G, McKenzie Katja U S, Whitworth Judith A
High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
J Hypertens. 2003 Aug;21(8):1513-8. doi: 10.1097/00004872-200308000-00015.
To investigate the effects of the antioxidant Tempol on prevention and reversal of adrenocorticotrophic hormone (ACTH)-induced hypertension in the rat, a model of hypertension characterized by nitric oxide deficiency.
Male Sprague-Dawley rats (n = 10 in each group) were treated with either saline or ACTH (0.2 mg/kg per day, s.c.) for 12 days. Tempol (1 mmol/l in drinking water) treatment was started on either day 8 (T8) of ACTH or saline treatment (reversal study), or 4 days prior to ACTH or saline treatment (prevention study). Systolic blood pressure (SBP) was measured using tail-cuff sphygmomanometry. Plasma F2-isoprostanes, a marker of oxidative stress, were measured by gas chromatography-mass spectrometry.
ACTH increased SBP (mean +/- SEM: 119 +/- 5 to 147 +/- 7 mmHg, P < 0.0005) and plasma F2-isoprostane concentration (8.4 +/- 1.2 saline versus 12.9 +/- 1.6 nmol/l ACTH, P < 0.05). Tempol alone did not alter SBP, but administration of Tempol on T8 reversed ACTH-induced hypertension (from 134 +/- 4 T8 to 118 +/- 3 mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 +/- 2 mmHg, P' < 0.05). However, Tempol had no effect on F2-isoprostane concentrations at the dose used in this study.
ACTH-induced hypertension in the rat is associated with increased oxidative stress. Tempol treatment reversed, and pretreatment partially prevented ACTH-induced hypertension, independent of improvement in systemic oxidative stress.
研究抗氧化剂Tempol对一氧化氮缺乏所致高血压模型大鼠中促肾上腺皮质激素（ACTH）诱导的高血压的预防及逆转作用。
雄性Sprague-Dawley大鼠（每组n = 10）接受生理盐水或ACTH（0.2 mg/kg每日，皮下注射）处理12天。在ACTH或生理盐水处理的第8天（T8）开始给予Tempol（饮水中含1 mmol/l）处理（逆转研究），或在ACTH或生理盐水处理前4天开始（预防研究）。使用尾套式血压计测量收缩压（SBP）。通过气相色谱-质谱法测量氧化应激标志物血浆F2-异前列腺素。
ACTH使SBP升高（均值±标准误：从119±5至147±7 mmHg，P < 0.0005）以及血浆F2-异前列腺素浓度升高（生理盐水组8.4±1.2对比ACTH组12.9±1.6 nmol/l，P < 0.05）。单独使用Tempol未改变SBP，但在T8给予Tempol可逆转ACTH诱导的高血压（从T8时的134±4降至118±3 mmHg，P < 0.005）。Tempol预处理可部分预防ACTH诱导的高血压（123±2 mmHg，P' < 0.05）。然而，本研究中所用剂量的Tempol对F2-异前列腺素浓度无影响。
大鼠中ACTH诱导的高血压与氧化应激增加相关。Tempol治疗可逆转，且预处理可部分预防ACTH诱导的高血压，与全身氧化应激改善无关。
