Role of reactive oxygen species in hypertension produced by reduced uterine perfusion in pregnant rats

Abstract

Background: Although recent studies indicate preeclampsia (PE) is associated with increased oxidative stress, the role of reactive oxygen species in the hypertension associated with PE remains unclear. We sought to test the hypothesis that placental ischemia increases oxidative stress which in turn, contributes to hypertension.

Methods: Reduction in uterine perfusion pressure (RUPP) was induced by placing silver clips on the abdominal aorta and the ovarian arteries on day 14 of pregnancy. On day 20 of pregnancy, mean arterial pressure (MAP) was measured and oxidative stress was assessed in renal and placental tissues whereas systemic administration of tempol, a superoxide dismutase (SOD) mimetic, was used to evaluate the contribution of reactive oxygen species on RUPP-induced hypertension.

Results: MAP (120 +/- 2 mm Hg vs.106 +/- 3 mm Hg), placental levels of 8-isoprostane (1.9 +/- 0.4 ng/g tissue vs. 0.8 +/- 0.1 ng/g tissue), and malondialdehyde (MDA) (6.9 +/- 0.6 micromol/g tissue vs. 3.9 +/- 0.4 micromol/g tissue) were increased, whereas renal cortical SOD activity was decreased in RUPP rats (1.2 +/- 0.1 units/mg protein vs. 1.6 +/- 0.1 units/mg protein) at day 20 of gestation (20 dG) compared to controls. Chronic treatment with tempol attenuated the hypertension (RUPP + tempol 112 +/- 2 mm Hg vs. RUPP, 120 +/- 2 mm Hg) associated with RUPP, whereas tempol had no effect on MAP (NP, 106 +/- 3 vs. NP + tempol, 108 +/- 2) in control rats.

Conclusion: The results of this study indicate that placental ischemia decreases innate antioxidant activity resulting in elevated oxidative stress which appears to play a role in mediating hypertension associated with chronic RUPP in pregnant rats.

Figure 1

Mean arterial pressure (MAP) in late gestation rats. Reduced uterine perfusion pressure (RUPP; n = 15) increased MAP compared to normal pregnant (NP; n = 11) control rats, whereas treatment with tempol in the RUPP group (RUPP + T; n = 13) attenuated the increased MAP but had no effect in the normal pregnant + tempol rats (NP + T; n = 10). All data are expressed as mean ± s.e.m. *P < 0.001 RUPP vs. NP rats; ^#P < 0.05 RUPP + T vs. RUPP.

Figure 2

Changes in placental isoprostane, malondialdehyde (MDA) and superoxide in response to chronic RUPP. (a) Placental isoprostane, (b) MDA, and (c) superoxide were increased (P < 0.05) in the RUPP (n = 12) compared to the NP (n = 10) dams. *P < 0.05 RUPP vs. NP. All data are expressed as mean ± s.e.m.