Adrenergic receptor blockade attenuates placental ischemia-induced hypertension

Physiol Rep. 2018 Sep;6(17):e13814. doi: 10.14814/phy2.13814.

Abstract

Preeclampsia (PE), a disorder of new-onset maternal hypertension and vascular dysfunction during pregnancy, is thought to be linked to placental ischemia-induced release of prohypertensive factors and reductions of vasoprotective factors in the maternal circulation. Although markers of sympathetic nervous activity are elevated in experimental models of placental ischemia-induced hypertension and women with PE compared with their normal pregnant counterparts, the importance of adrenergic receptor signaling in the development of hypertension in PE is unknown. Therefore, we tested the hypothesis that adrenergic receptor blockade attenuates the development of placental ischemia-induced hypertension in rats. Wistar Hannover rats underwent reduced uterine perfusion pressure (RUPP) or Sham surgeries on gestational day 14. By day 19, mean arterial blood pressure (MAP) was increased in RUPP over Sham rats. Groups of RUPP and Sham pregnant rats received terazosin and propranolol (3 mg/kg per day of each via subcutaneous osmotic minipump) to block α1- and β-adrenergic receptors, respectively, beginning on gestational day 14. Adrenergic blockade significantly attenuated the development of hypertension in the RUPP rats with a slight blood pressure-lowering response in the Sham, normal pregnant rats by day 19. In conclusion, these data implicate that placental ischemia-induced hypertension involves adrenergic receptor signaling to promote increases in blood pressure during PE.

Keywords: RUPP; PlGF; Placenta; preeclampsia; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists / administration & dosage
  • Adrenergic alpha-1 Receptor Antagonists / therapeutic use*
  • Adrenergic beta-Antagonists / administration & dosage
  • Adrenergic beta-Antagonists / therapeutic use*
  • Animals
  • Blood Pressure
  • Female
  • Ischemia / complications
  • Placenta / blood supply
  • Prazosin / administration & dosage
  • Prazosin / analogs & derivatives*
  • Prazosin / therapeutic use
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / etiology
  • Pregnancy
  • Propranolol / administration & dosage
  • Propranolol / therapeutic use*
  • Rats
  • Rats, Wistar

Substances

  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic beta-Antagonists
  • Terazosin
  • Propranolol
  • Prazosin