Arachidonic Acid Metabolism in Glucocorticoid-Induced Hypertension

Abstract

1. Products of metabolism of arachidonic acid, such as 20- hydroxyeicosatetraenoic acid (20-HETE), thromboxane A2 (TXA 2) and prostaglandin I2 (PGI2), 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 TXA2 and PGI2 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, TXA2 and PGI2 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 PGI2 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 PGI2 were unchanged in both models of glucocorticoid-hypertension. The vasoconstrictor 20-HETE may play a role in the genesis of ACTH-induced hypertension.