Key result
Chronic AT1-AA infusion raises MAP by ~15 mm Hg in pregnant rats.
Why the study?
Does tempol reduce hypertension and placental oxidative stress in AT1-AA-induced hypertensive pregnant rats?
Does tempol reduce hypertension and placental oxidative stress in AT1-AA-induced hypertensive pregnant rats?
Absolute Event Rate: 116% vs 101%
p-value: p=0.002
AT1-AA contributes to placental oxidative stress, mediating hypertension during pregnancy, which can be mitigated by the superoxide dismutase mimetic tempol.
May implicate AT1-AA–ROS pathway in gestational hypertension; leaves open clinical translation to human preeclampsia.
BACKGROUND: Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) and reactive oxygen species (ROS) are implicated in the pathophysiology of preeclampsia. The objective of this study was to determine the role of AT1-AA to stimulate placental oxidative stress in vivo and role ROS in mediating hypertension in response to AT1-AA during pregnancy. METHODS: To achieve these goals, blood pressure (mean arterial pressure (MAP)) and ROS were analyzed in AT1-AA-induced hypertensive pregnant rats in the presence and absence of a superoxide dismutase mimetic, tempol. Rat AT1-AA (1:50) and tempol (30 mg/kg/day) were administered to pregnant rats beginning on day 12 of gestation. On day 19, MAP was analyzed and tissues collected for ROS analysis via lucigenin chemiluminescence. RESULTS: MAP increased from 101 ± 2 normal pregnant (NP) rats to 116 ± 2 mm Hg in chronic AT1-AA infused rats (P = 0.002). Placental basal and NADPH oxidase stimulated ROS was 29 ± 6 and 92 ± 10 relative light units (RLUs) in NP rats. These levels increased to 159 ± 29 (P < 0.0001) and 287 ± 60 RLUs (P < 0.006) in AT1-AA infused rats. MAP in AT1-AA + tempol rats was 109 ± 2 mm Hg, no difference than tempol-treated controls (109 ± 3 mm Hg). Administration of tempol decreased basal and NADPH-stimulated placental ROS in AT1-AA-treated rats (121 ± 13; 262 ± 21 RLUs). Basal and NADPH-stimulated ROS in tempol-treated controls were 69 ± 24; 141 ± 33 RLUs. CONCLUSION: This study indicates that AT1-AA's contribute to placental oxidative stress; one mechanism whereby the AT1-AA mediates hypertension during pregnancy.
No takes yet. Share an insight, caveat, or question.
Parrish et al. (2011) studied Pregnancy-Induced Hypertension. AT1-AA infusion vs. Normal pregnant rats was evaluated on Mean arterial pressure (MAP) (p=0.002). Chronic AT1-AA infusion in pregnant rats significantly increased mean arterial pressure to 116 mm Hg compared to 101 mm Hg in normal pregnant rats (P=0.002).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: