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Functional changes in the uterine artery precede the hypertensive phenotype in a transgenic model of hypertensive pregnancy

Authors

  • V.M. Pulgar
  • L.M. Yamaleyeva
  • J. Varagic
  • C. McGee
  • M. Bader
  • R. Dechend
  • K.B. Brosnihan

Journal

  • American Journal of Physiology Endocrinology and Metabolism

Citation

  • Am J Physiol Endocrinol Metab 309 (9): E811-E817

Abstract

  • The pregnant female human angiotensinogen (hAGN) transgenic rat mated with the male human renin (hREN) transgenic rat (TgA) is a model of preeclampsia with increased blood pressure, proteinuria, and placenta alterations of edema and necrosis at late gestation. We studied vascular responses and the role of COX-derived prostanoids in the uterine artery (UA) at early gestation in this model. TgA UA showed lower stretch response, similar smooth muscle alpha-actin content and lower collagen content compared to Sprague-Dawley (SD) UA. Vasodilation to acetylcholine was similar in SD and TgA UA (64+/-8 vs. 75+/-6% of relaxation; p>0.05) with an acetylcholine-induced contraction in TgA UA that was abolished by pre-incubation with indomethacin (78+/-6 vs. 83+/-11%, p>0.05). No differences in the contraction to phenylephrine were observed (159+/-11 vs. 134+/-12 %KMAX, p>0.05), although in TgA UA this response was greatly affected by pre-incubation with indomethacin (179+/-16 vs. 134+/-9 %KMAX, p<0.05; pD2 5.92+/-0.08 vs. 5.85+/-0.03, p<0.05). Endothelium-independent vasodilation was lower in TgA UA (92+/-2 vs. 74+/-5 % pre-constricted tone, p<0.05) and pre-incubation with indomethacin restored the response to normal values (90+/-3 vs. 84+/-3%). Immunostaining showed similar signals for alpha-actin, COX-2 and eNOS between groups (p>0.05). Plasma thromboxane levels were similar between groups. In summary, TgA UA displays functional alterations at early gestation, before the preeclamptic phenotype is established. Inhibition of COX enzymes normalizes some of the functional defects in the TgA UA. An increased role for COX-derived prostanoids in this model of preeclampsia may contribute to the development of a hypertensive pregnancy.


DOI

doi:10.1152/ajpendo.00526.2014