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N ‐ACETYLCYSTEINE PREVENTS BUT DOES NOT REVERSE DEXAMETHASONE‐INDUCED HYPERTENSION
Author(s) -
Krug Susanne,
Zhang Yi,
Mori Trevor A,
Croft Kevin D,
Vickers Janine J,
Langton Leanne K,
Whitworth Judith A
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.04947.x
Subject(s) - acetylcysteine , dexamethasone , saline , endocrinology , medicine , blood pressure , glucocorticoid , chemistry , antioxidant , biochemistry
SUMMARY1 We have shown previously that N ‐acetylcysteine (NAC) prevents the increase in blood pressure induced by adrenocorticotropin treatment. The present study investigated the effect of NAC on dexamethasone (Dex)‐induced hypertension. 2 Male Sprague‐Dawley rats were randomly divided into six groups ( n = 10 in each). In a prevention study, NAC (10 g/L in the drinking water) was given for 4 days prior to and 11 days during concurrent treatment with saline (0.1 mL/rat per day) or with Dex (10 mg/rat per day). In a reversal study, daily injections of Dex or saline began 8 days before NAC and cotreatment continued for 5 days. Systolic blood pressure (SBP) was measured on alternate days using a tail‐cuff system. 3 Dexamethasone significantly increased SBP from 113 ± 4 to 139 ± 6 mmHg ( n = 10; P < 0.01). N ‐Acetylcysteine alone had no effect on SBP. In NAC + Dex‐treated rats, SBP was significantly lower than that of Dex‐treated rats ( P¢ < 0.01). In fully established Dex‐hypertension NAC was ineffective and SBP remained high. 4 Both Dex and NAC treatments decreased bodyweight gain. N ‐Acetylcysteine reduced food and water consumption. Dexamethasone reduced thymus weight ( P¢ < 0.01) but NAC treatment did not alter this marker of glucocorticoid activity. 5 Dexamethasone tended to decrease plasma NO x , whereas NAC restored plasma NO x concentrations to control levels. N ‐Acetylcysteine had no effect on Dex‐induced increased plasma F 2 ‐isoprostane concentrations. 6 In conclusion, NAC partially prevented, but did not reverse, Dex‐induced hypertension.