TY - JOUR
T1 - The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat
AU - Zhang, Yi
AU - Jang, Ryan
AU - Mori, Trevor A.
AU - Croft, Kevin D.
AU - Schyvens, Christopher G.
AU - McKenzie, Katja U.S.
AU - Whitworth, Judith A.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Objective: 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. Methods: 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. Results: 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 ± mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 ± 2 mmHg, P′ < 0.05). However, Tempol had no effect on F 2-isoprostane concentrations at the dose used in this study. Conclusions: 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.
AB - Objective: 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. Methods: 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. Results: 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 ± mmHg, P < 0.005). Tempol pre-treatment partially prevented ACTH-induced hypertension (123 ± 2 mmHg, P′ < 0.05). However, Tempol had no effect on F 2-isoprostane concentrations at the dose used in this study. Conclusions: 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.
KW - Adrenocorticotrophic hormone
KW - Antioxidants
KW - Blood pressure
KW - F -isoprostanes
KW - Tempol
UR - http://www.scopus.com/inward/record.url?scp=0042991271&partnerID=8YFLogxK
U2 - 10.1097/00004872-200308000-00015
DO - 10.1097/00004872-200308000-00015
M3 - Article
SN - 0263-6352
VL - 21
SP - 1513
EP - 1518
JO - Journal of Hypertension
JF - Journal of Hypertension
IS - 8
ER -