TY - JOUR
T1 - Angiotensin ii induces renal oxidant stress in vivo and heme oxygenase-1 in vivo and in vitro
AU - Haugen, Eric N.
AU - Croatt, Anthony J.
AU - Nath, Karl A.
PY - 2000
Y1 - 2000
N2 - Background: Angiotensin II is strongly incriminated in progressive renal injury. There is recent evidence that angiotensin II induces oxidative stress in vitro. We examined the capacity of angiotensin II to induce oxidative stress in vivo and the functional significance of such stress. The capacity of angiotensin II to induce the oxidant-sensitive gene heme oxygenase (HO) in vivo and in vitro was also examined. Methods: Angiotensin II was administered via mini-osmotic pumps to rats maintained on standard diets. Indices of oxidative stress, including thiobarbituric acid reactive substance, carbonyl protein content, and HO activity, were determined. Indices of oxidative stress and functional markers were also determined in the DOCA salt model. The effect of angiotensin II was studied in rats maintained on antioxidant- deficient diets so as to examine the functional significance of oxidative stress induced by angiotensin II. We also explored the inductive effect of angiotensin II on HO in vivo and whether such actions occur in vitro. Results: Angiotensin II administered in vivo increased kidney content of thiobarbituric acid reactive substances protein carbonyl content, and HO activity. These indices were not present in the kidney of rats treated with DOCA salt for three weeks. Such oxidative stress was functionally significant, since the administration of angiotensin II to rats maintained on a prooxidant diet demonstrated increased proteinuria and decreased creatinine clearance. The stimulatory effect on HO activity was due to induction of HO-1 mRNA, with HO-2 mRNA remaining unchanged. Expression of HO-1 was localized to the renal proximal tubules in vivo. We also demonstrate that angiotensin II at concentrations of 10-8 and 10-7 mol/L induces expression of HO-1 mRNA in LLC-PK1 cells. Conclusions: Angiotensin II induces oxidative stress in vivo, which contributes to renal injury. This study also demonstrates that angiotensin II induces renal HO activity caused by upregulation of HO-1 in renal proximal tubules. Finally, angiotensin II directly induces HO-1 in renal proximal tubular epithelial cells in vitro.
AB - Background: Angiotensin II is strongly incriminated in progressive renal injury. There is recent evidence that angiotensin II induces oxidative stress in vitro. We examined the capacity of angiotensin II to induce oxidative stress in vivo and the functional significance of such stress. The capacity of angiotensin II to induce the oxidant-sensitive gene heme oxygenase (HO) in vivo and in vitro was also examined. Methods: Angiotensin II was administered via mini-osmotic pumps to rats maintained on standard diets. Indices of oxidative stress, including thiobarbituric acid reactive substance, carbonyl protein content, and HO activity, were determined. Indices of oxidative stress and functional markers were also determined in the DOCA salt model. The effect of angiotensin II was studied in rats maintained on antioxidant- deficient diets so as to examine the functional significance of oxidative stress induced by angiotensin II. We also explored the inductive effect of angiotensin II on HO in vivo and whether such actions occur in vitro. Results: Angiotensin II administered in vivo increased kidney content of thiobarbituric acid reactive substances protein carbonyl content, and HO activity. These indices were not present in the kidney of rats treated with DOCA salt for three weeks. Such oxidative stress was functionally significant, since the administration of angiotensin II to rats maintained on a prooxidant diet demonstrated increased proteinuria and decreased creatinine clearance. The stimulatory effect on HO activity was due to induction of HO-1 mRNA, with HO-2 mRNA remaining unchanged. Expression of HO-1 was localized to the renal proximal tubules in vivo. We also demonstrate that angiotensin II at concentrations of 10-8 and 10-7 mol/L induces expression of HO-1 mRNA in LLC-PK1 cells. Conclusions: Angiotensin II induces oxidative stress in vivo, which contributes to renal injury. This study also demonstrates that angiotensin II induces renal HO activity caused by upregulation of HO-1 in renal proximal tubules. Finally, angiotensin II directly induces HO-1 in renal proximal tubular epithelial cells in vitro.
KW - Chronic renal injury
KW - Hemodynamics
KW - Renal tubule
KW - Systemic hypertension, proteinuria
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U2 - 10.1046/j.1523-1755.2000.00150.x
DO - 10.1046/j.1523-1755.2000.00150.x
M3 - Article
C2 - 10886559
AN - SCOPUS:0033922326
SN - 0085-2538
VL - 58
SP - 144
EP - 152
JO - Kidney international
JF - Kidney international
IS - 1
ER -