Premium
Preeclampsia alters the role of nitric oxide in androgen metabolite‐induced vasorelaxation of rat uterine artery
Author(s) -
Hanson Andrea E.,
McKenna Joshua M.,
Garcia Nikolas W.,
Perusquia Mercedes,
Stallone John N.
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.584.8
Subject(s) - endocrinology , medicine , myograph , dihydrotestosterone , nitric oxide , chemistry , preeclampsia , metabolite , androgen , vasodilation , placenta , agonist , pregnancy , fetus , biology , receptor , hormone , genetics
Preeclampsia (PE) is a pregnancy‐induced disorder and a major cause of both fetal and maternal morbidity and mortality. During pregnancy, the placenta produces abundant androgens, and these rapid, non‐genomic vasodilators may serve to maintain uterine blood flow during normal pregnancy and may be impaired in PE. Of the known placental androgens, testosterone (TES) and its genomically inactive metabolite, 5β‐dihydrotestosterone (5β‐DHT), were previously reported to induce vasorelaxation in uterine arteries (UA). This study aimed to determine the nitric oxide (NO) signaling mechanisms involved in TES‐ and 5β‐DHT‐ induced relaxation in the rat UA using the DOCA‐salt model of PE. Endothelium‐intact UA rings (200 μm, dia.) from normal pregnant (NP) and DOCA‐treated pregnant (DSP) female (F) Sprague‐Dawley rats (250–300g) were prepared for measurements of isometric contractile force (DMT myograph). UA were pretreated with L‐N G ‐monomethyl arginine citrate (L‐NMMA, 100 μM), a non‐selective nitric oxide synthase (NOS) inhibitor or N W ‐propyl‐L‐arginine (200 nM), a specific nNOS inhibitor. UA were then precontracted with U‐46619 (thromboxane A2 agonist, 1 μM) and a concentration‐dependent relaxation to TES and 5β‐DHT was obtained (0.1–1000 nM). Data are means ± SE (n = 6 rats). Androgen‐induced maximal UA relaxation was reduced by L‐NMMA in NP (TES: 33.84 ± 4.6 vs. 1.24 ± 4.0 and 5β‐DHT: 28.12 ± 6.1 vs. 2.0 ± 6.3) and in DSP (TES: 36.23 ± 4.6 vs. 4.44 ± 2.3 and 5β‐DHT: 30.71 ± 4.6 vs. 0.9 ± 2.4). Maximal relaxation was reduced by N W ‐propyl‐L‐arginine in NP for both TES (24.53 ± 6.1) and 5β‐DHT (20.38 ± 3.8) and in DSP for 5β‐DHT (18.78 ± 6.7); however TES induced UA relaxation was unchanged with N W ‐propyl‐L‐arginine in DSP (33.60 ± 10.4). These data suggest that: 1) androgen‐induced UA relaxation is both nNOS and eNOS dependent in NP; and 2) nNOS dependent TES‐induced relaxation of UA is decreased in DSP. (State of Texas) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .