The anti-oxidant Tempol reverses and partially prevents adrenocorticotrophic hormone-induced hypertension in the rat.
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 +/- 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.


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.
Zhang
Yi
Y
High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Jang
Ryan
R
Mori
Trevor A
TA
Croft
Kevin D
KD
Schyvens
Christopher G
CG
McKenzie
Katja U S
KU
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D028441:F2-Isoprostanes / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000494:pharmacology; D013113:Spin Labels
D000975:Antioxidants; D003497:Cyclic N-Oxides; D028441:F2-Isoprostanes; D013113:Spin Labels; D009569:Nitric Oxide; D012965:Sodium Chloride; D000324:Adrenocorticotropic Hormone; C001803:tempol