(Hypertension. 2001;38:655.)
© 2001 American Heart Association, Inc.
Renin-Angiotensin System |
Antioxidants Block Angiotensin II-Induced Increases in Blood Pressure and Endothelin
Department of Physiology and Biophysics (M.C.O., M.C.M., J.C.R., L.A.J.) and Division of Nephrology (L.A.J.), Mayo School of Medicine, Mayo Clinic, Rochester, Minn
Correspondence to Luis A Juncos, Division of Nephrology, Mayo Clinic, Guggenheim Bldg 942A, 200 First St SW, Rochester, MN 55905. E-Mail Juncos.Luis{at}Mayo.Edu
Abstract
Abstract—— Chronically infusing a subpressor dose of angiotensin (Ang) II increases blood pressure via poorly defined mechanisms. We found that this hypertensive response is accompanied by increased oxidant stress and is prevented by blocking endothelin (ET) receptors. Thus, we now tested whether blocking oxidant stress decreases both blood pressure and ET levels. We infused Sprague-Dawley rats (via osmotic pumps) with either vehicle (group 1) or Ang II (5 ng · kg-1 · min-1; groups 2 to 4) for 15 days. Groups 3 and 4 also received either tempol in the drinking water (1 mmol/L) or vitamin E (5000 IU/kg diet), respectively, for 15 days. We measured systolic blood pressure (SBP) and urinary nitrite excretion every 3 days, and on day 15 we measured systemic and renal venous plasma levels of ET, isoprostanes, and thiobarbituric acid reactive substances (TBARS). SBP in Group 1 did not change throughout the study, whereas Ang II increased SBP (from 132±5 to 151±7 mm Hg). In addition, Ang II increased the systemic and renal venous levels of isoprostanes, TBARS, and ET and caused a transient decrease in urinary nitrites (that returned to control levels by day 9). Both tempol and vitamin E prevented Ang II-induced hypertension and either prevented or tended to blunt the increase in systemic and renal isoprostanes, TBARS, and ET. Finally, both antioxidants abolished the transient decrease in urinary nitrites. These results together with our previous study suggest that subpressor-dose Ang II increases oxidant stress (and isoprostanes). This in turn increases ET levels, which participate in the hypertensive response to Ang II.
Key Words: angiotensin II • renal blood flow • free radicals • oxidative stress • hypertension, arterial • kidney • antioxidants
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