Role of Endothelin and Isoprostanes in Slow Pressor Responses to Angiotensin II

Abstract

—We tested the hypothesis that angiotensin II (Ang II)‐induced stimulations of endothelin (ET) and isoprostanes are implicated in the slow pressor responses to Ang II. We infused either vehicle (group 1) or Ang II (groups 2 to 4) intravenously at 5 ng/kg per minute via osmotic pumps,for 15 days into Sprague-Dawley rats. Groups 3 and 4 received 30 mg/kg per day of either losartan (Ang II type 1 receptor blocker) or bosentan (ETA and ETB receptor blocker) in their drinking water. We measured systolic blood pressure (SBP) every 3 days during the infusion. Plasma levels of Ang II, ET, isoprostanes, and urinary nitrites were determined at 15 days. Vehicle infusion did not change SBP (from 138613 to 13662 mm Hg at day 15). Circulating Ang II, ET, and isoprostane levels were 3569, 3963, and 111610 pg/mL, respectively, whereas urinary nitrites were 2.360.4 mg/d. Ang II increased SBP (from 133610 to 15868 mm Hg), plasma Ang II (179677 pg/mL), and isoprostanes (156619 pg/mL) without altering ET levels (3865 pg/mL) or urinary nitrites (1.860.5 mg/d). Losartan prevented Ang II‐induced increases in SBP and isoprostanes (SBP went from 13765 to 12064 mm,Hg; isoprostanes were 115615 pg/mL) while increasing urinary nitrite levels (5.261.1 mg/d). Losartan