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ARACHIDONIC ACID METABOLISM IN GLUCOCORTICOID‐INDUCED HYPERTENSION
Author(s) -
Zhang Yi,
Hu Lexian,
Mori Trevor A,
Barden Anne,
Croft Kevin D,
Whitworth Judith A
Publication year - 2007
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.1440-1681.2007.04839.x
Subject(s) - endocrinology , medicine , creatinine , glucocorticoid , dexamethasone , chemistry , arachidonic acid , thromboxane b2 , excretion , saline , thromboxane a2 , biochemistry , platelet , enzyme
SUMMARY1 Products of metabolism of arachidonic acid, such as 20‐hydroxyeicosatetraenoic acid (20‐HETE), thromboxane A 2 (TXA 2 ) and prostaglandin I 2 (PGI 2 ), regulate vascular tone. Among them, 20‐HETE is a potent constrictor in small arteries that also has natriuretic properties. The present study investigated changes in urinary concentrations of 20‐HETE and metabolites of TXA 2 and PGI 2 in glucocorticoid‐hypertension in rats, a sodium‐independent model. 2 Male Sprague‐Dawley rats were treated with saline, adrenocorticotrophic hormone (ACTH; 0.2 mg/kg) or dexamethasone (20 µg/kg) by daily s.c. injection for 12 days. Systolic blood pressure (SBP) was measured using the tail‐cuff method. Metabolic cages were used for 24 h urine collection. Thymus weight and urinary concentrations of 20‐HETE, TXA 2 and PGI 2 were determined. 3 In the present study, SBP was increased by both ACTH (from 102 ± 2 to 134 ± 7 mmHg; n = 10; P < 0.01) and dexamethasone (from 106 ± 5 to 122 ± 4 mmHg; n = 10; P < 0.01). Thymus weight, a marker for glucocorticoid activity, was significantly decreased by both ACTH and dexamethasone (56 ± 9 and 76 ± 5 mg/100 g bodyweight, respectively; n = 10; P ′ < 0.01) compared with the saline control (151 ± 5 mg/100 g bodyweight; n = 20). Urinary 20‐HETE excretion was increased by ACTH (501 ± 115 pmol/g creatinine; n = 10; P ′ < 0.05) but not by dexamethasone (126 ± 13 pmol/g creatinine; n = 10) compared with the saline control (219 ± 54 pmol/g creatinine; n = 20). Neither ACTH nor dexamethasone affected urinary excretion of TXB 2 or PGI 2 compared with the saline control. 4 In conclusion, ACTH but not dexamethasone increased urinary 20‐HETE excretion in male Sprague‐Dawley rats. Urinary concentrations of the metabolites TXB 2 and PGI 2 were unchanged in both models of glucocorticoid‐hypertension. The vasoconstrictor 20‐HETE may play a role in the genesis of ACTH‐induced hypertension.