Role of endothelin and isoprostanes in slow pressor responses to angiotensin II

被引:62
作者
Ortiz, MC
Sanabria, E
Manriquez, MC
Romero, JC
Juncos, LA
机构
[1] Mayo Clin & Mayo Fdn, Div Nephrol, Rochester, MN 55905 USA
[2] Mayo Med Sch, Dept Physiol & Biophys, Rochester, MN USA
[3] Mayo Med Sch, Div Nephrol, Rochester, MN USA
关键词
blood pressure; free radicals; hypertension; arterial; kidney; losartan;
D O I
10.1161/01.HYP.37.2.505
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
We tested the hypothesis that angiotensin II (Ang II)-induced stimulations of endothelin (ET) and isoprostanes are implicated in the slow presser 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 138+/-13 to 136+/-2 mm Hg at day 15), Circulating Ang II, ET, and isoprostane levels were 35+/-9, 39+/-3, and 111+/-10 pg/mL, respectively, whereas urinary nitrites were 2.3+/-0.4 mug/d. Ang II increased SBP (from 133+/-10 to 158+/-8 mm Hg), plasma Ang II (179+/-77 pg/mL), and isoprostanes (156+/-19 pg/mL) without altering ET levels (38+/-5 pg/mL) or urinary nitrites (1.8+/-0.5 mug/d). Losartan prevented Ang II-induced increases in SBP and isoprostanes (SBP went from 137+/-5 to 120+/-4 mm Hg; isoprostanes were 115+/-15 pg/mL) while increasing urinary nitrite levels (5.2+/-1.1 mug/d). Losartan did not alter Ang II (141+/-57 pg/mL) or ET (40+/-4 pg/mL) levels. Bosentan also blocked Ang II-induced hypertension (from 135+/-4 to 139+/-3 mm Hg) but did not decrease isoprostanes (146+/-14 pg/mL). Ang II (63+/-11 pg/mL), ET levels (46+/-2 pg/mL), and urinary nitrites (2.8+/-0.4 mug/d) were not altered. In conclusion, our results suggest that low-dose Ang II increases isoprostanes via its Ang II type 1 receptor and causes an ET-dependent hypertension, without altering circulating ET levels.
引用
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页码:505 / 510
页数:6
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