Arachidonic acid metabolism in glucocorticoid-induced hypertension.
1. 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 microg/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.
Zhang
Yi
Y
The High Blood Pressure Research Unit, The John Curtin School of Medical Research, The Australian National University, Canberra, Australian Capital Territory, Australia.
Hu
Lexian
L
Mori
Trevor A
TA
Barden
Anne
A
Croft
Kevin D
KD
Whitworth
Judith A
JA
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D051381:Rats; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects
D005938:Glucocorticoids; D016718:Arachidonic Acid; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone