Temporal changes in eicosanoid excretion in Angiotensin (A) II‐induced hypertension

The 10‐day AII infusion model of hypertension alters arachidonic acid metabolism involving 1) adenosine‐stimulated epoxyeicosatrienoic acid (EETs) synthesis and 2) tumor necrosis factor (TNF)‐activated COX‐2‐PGE 2 mechanisms. Male Sprague‐Dawley rats (age 8‐10 weeks) were infused with AII (125 ng/min); sham control rats received 0.01 N acetic acid. Day 3 values: systolic blood pressure (SBP): AII 195±11 vs. Sham 123±4 mmHg; urinary excretion of EETs increased to AII 8.9±3.7 vs. Sham 1.7±0.3 ng/d (p<0.05). Peak EET excretion coincided with increased adenosine excretion: AII 3.86±1.0 vs. Sham 0.79±0.2 adenosine/internal standard ratio (p<0.05). Urinary TNF excretion: AII 466±106 vs. Sham 80±26 pg/d (p<0.05); PGE 2 excretion: AII 389±94 vs. Sham 140±20 ng/d. Day 10 values: SBP: AII 184±5 vs. Sham 120±5 mmHg; EETs excretion fell to levels not different from those of Sham. TNF and PGE 2 excretion remain elevated: AII 457±12 vs. Sham 41±11 pg/d; AII 645±143 vs. Sham 237±44 ng/d, respectively (p<0.05). The role of heme oxygenase‐1 (HO‐1) in producing a decline in EET production in rats receiving AII was examined. Rats were infused with subpressor concentrations of AII (40 ng/min) for 3 days with and without concurrent SnCl 2 treatment to induce HO‐1. SnCl 2 treatment produced diminished release of EETs from isolated kidneys (AII 8.3±3.8 vs. AII + SnCl 2 0.29±0.27 ng/min). Features of the 10‐day AII infusion model of hypertension are: 1) initial rise and late decline in EET production; the latter possibly via activation of HO‐1 and 2) sustained increased PGE 2 excretion.