Progesterone supplementation attenuates hypertension and the autoantibody to the angiotensin II type I receptor in response to elevated interleukin-6 during pregnancy

Autor/innen

  • L.M. Amaral
  • L. Kipprono
  • D.C. Cornelius
  • C. Shoemaker
  • K. Wallace
  • J. Moseley
  • G. Wallukat
  • J.N. Martin
  • R. Dechend
  • B. Lamarca

Journal

  • American Journal of Obstetrics and Gynecology

Quellenangabe

  • Am J Obstet Gynecol 211 (2): 158.e1-158.e6

Zusammenfassung

  • BACKGROUND: Preeclampsia is a multi-system disorder recognized as hypertension with proteinuria developing after 20 weeks gestation. Preeclampsia is associated with chronic immune activation characterized by increased T and B lymphocytes, cytokines and antibodies activating the angiotensin II type I receptor (AT1-AA). Hypertension in response to elevated Interleukin 6 (IL-6) during pregnancy occurs with increased renin activity, AT1-AA and reduced kidney function. STUDY DESIGN: We aim to determine whether 17-alpha-hydroxyprogesterone caproate (17-OHPC), progesterone, improved inflammatory pathways during elevated IL-6 in pregnant rats. IL-6 (5ng/day) was infused via miniosmotic pumps into normal pregnant rats (NP) beginning on day 14 of gestation and 17-OHP (3.32mg/kg) was diluted in normal saline and injected on day 18. Blood pressure (MAP) determination and serum collection were performed on day 19 of gestation. RESULTS: MAP in NP was 100+3mmHg which increased with IL-6 to 112+4mmHg, p <0.05. Pregnant rats given 17-OHP alone had a MAP of 99+3mmHg and MAP increased to 103+2 mmHg in IL-6+17-OHP. AT1-AA was 1.2+0.5 bpm in NP rats, increased to 17+9 bpm with IL-6 infusion but administration of 17-OHP significantly blunted AT1-AA to 4+0.8bpm in NP+IL-6+17-OHP. Total circulating nitrate/nitrite was significantly decreased and placental Ser1177-P-eNOS/eNOS was lowered with IL-6 infusion. 17 OHP supplementation significantly improved placental Ser1177-P-eNOS/eNOS however, circulating nitrate/nitrite was unchanged with 7OHPC supplementation. CONCLUSION: This study illustrates that 17-OHP attenuated hypertension, decreased AT1-AA activity and improved placental nitric oxide in response to elevated IL-6 during pregnancy and could lend hope to a new potential therapeutic for preeclampsia.


DOI

doi:10.1016/j.ajog.2014.02.018