title: Heme oxygenase inhibition increases blood pressure in pregnant rats.
abstract: BACKGROUND
  During normal gestation, the placenta is a relatively hypoxic organ and, as such, is subject to significant oxidative stress. In the preeclamptic patient, inadequate remodeling of the maternal vasculature severely exacerbates placental oxidative stress, which has been shown to be an important component of maternal hypertension. There is emerging evidence that Heme Oxygenase-1 (HO-1) acts as an important regulator of placental and cardiovascular function during normal pregnancy. Here, we have examined the effect of Heme Oxygenase (HO) inhibition in late gestation on maternal blood pressure, angiogenic balance, and placental oxidative stress in pregnant rats.
  
  
  METHODS
  HO activity was inhibited with tin mesoporphyrin (SnMP), which was administered on gestational day 14, and blood pressure was measured on gestational day 19. Placental angiogenic balance and plasma Vascular Endothelial Growth Factor (VEGF) were determined by sandwich enzyme-linked immunosorbent assay. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity was measured by lucigenin chemilluminescence.
  
  
  RESULTS
  In response to SnMP treatment, maternal mean arterial pressure (MAP) was significantly increased (99±1 vs. 113±2mm Hg; P < 0.05; n = 15 per group). Placental soluble fms-like tyrosine kinase-1 (sFlt-1) (631±47 vs. 648±26 pg/mg; P = 0.76) levels in the placenta were not affected by HO inhibition. Additionally, there was no significant difference in free VEGF in the maternal circulation (287±22 vs. 329±14 pg/ml; P = 0.11). There was, however, a significant decrease in placental VEGF (23±2 vs. 16±1 pg/mg; P < 0.05) and a significant increase in placental NADPH oxidase activity in SnMP-treated rats (2021±238 vs. 3005±301 RLU/min/mg; P < 0.05).
  
  
  CONCLUSIONS
  Our results demonstrate that HO is an important regulator of blood pressure and an important antioxidant in the developing placenta.
authors.affiliation: Department of Physiology and Biophysics and the Center for Excellence in Cardiovascular Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Eric M
authors.initials: EM
authors.lastname: George
authors.forename: Peter A
authors.initials: PA
authors.lastname: Hosick
authors.forename: David E
authors.initials: DE
authors.lastname: Stec
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018384:Oxidative Stress; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051547:Heme Oxygenase-1
keywords: NADPH oxidase; blood pressure; heme oxygenase; hypertension; preeclampsia; pregnancy; sFlt-1.
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