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Placental Ischemia‐Induced Hypertension Is Abolished by Adrenergic Receptor Blockade
Author(s) -
Spradley Frank T.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.729.8
Subject(s) - medicine , preeclampsia , phenylephrine , sympathetic nervous system , endocrinology , blood pressure , ischemia , fetus , vasoconstriction , perfusion , agonist , gestational hypertension , adrenergic receptor , placenta , pregnancy , receptor , biology , genetics
Hypertensive disorders of pregnancy are the number one cause of pregnancy‐related deaths in the United States. Preeclampsia is a disorder of maternal hypertension and vascular dysfunction presenting in the second half of pregnancy along with fetal growth restriction. Currently, there are no steadfast therapies besides early delivery of the fetus and ischemic placenta, which releases pro‐hypertensive factors into the maternal circulation. The sympathetic nervous system might be a novel target in treating preeclampsia, as sympathetic nervous activity is found to be increased in preeclamptic vs. normal pregnant women. However, it is unknown if the sympathetic nervous system mediates the development of placental ischemia‐induced hypertension. In this study, the hypothesis was tested that adrenergic receptor blockade prevents placental ischemia‐induced hypertension. Wistar Hannover rats were randomized to receive reduced uterine perfusion pressure (RUPP, N=15) or Sham RUPP (N=20) surgeries on gestational day 14 and examined at day 19. In RUPP vs. Sham rats, respectively, mean arterial blood pressure (MAP) was increased (121 ± 3 vs. 102 ± 1 mmHg, P<0.05) without a change in heart rate (421 ± 7 vs. 423 ± 4 bpm). Average fetal weights (1.87 ± 0.04 vs. 2.11 ± 0.03 g) and placental weights (0.50 ± 0.02 vs. 0.57 ± 0.01 g) were lower (P<0.05) in RUPP dams. In RUPP over Sham rats, vasoconstriction induced by the alpha‐adrenergic receptor agonist, phenylephrine, was greater in isolated renal interlobar arteries (Emax: 322 ± 19 vs. 251 ± 12 % of KCl response). The Emax response to KCl was not different between RUPP or Sham rats, in sequence: 100 ± 24 vs. 87 ± 14 % increase in force. A subset of RUPP (N=9) and Sham (N=9) rats received combined terazosin and propranolol (3 mg/kg per day of each, subcutaneous osmotic minipump) to block alpha‐ and beta‐adrenergic receptors, respectively, beginning the day of surgery on gestational day 14. By day 19, adrenergic blockade abolished the development of hypertension in RUPP rats (105 ± 2 mmHg, P<0.05) and reduced their heart rate (343 ± 21 bpm, P<0.05) with a lesser reduction detected in treated Sham rats for MAP (97 ± 2 mmHg, P<0.05) and heart rate (387 ± 9 bpm, P<0.05). Treatment did not alter average fetal weights (1.89 ± 0.05 and 2.11 ± 0.03 g) or placental weights (0.47 ± 0.02 and 0.50 ± 0.03 g) in RUPP and Sham rats, in turn, compared to their untreated counterparts. In conclusion, placental ischemia‐induced hypertension depends on activation of the sympathetic nervous system. The mechanisms responsible for this enhanced sympathetic nerve activity and adrenergic receptor signaling remain unknown but are likely to involve factors released from the ischemic placenta. Support or Funding Information 4R00HL130577‐02 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .