Cyclooxygenase-dependent mechanisms mediate in part the anti-dilatory effects of perivascular adipose tissue in uterine arteries from pregnant rats.

Autor: Osikoya O; Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, TX, USA., Cushen SC; Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, TX, USA., Ricci CA; Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, TX, USA., Goulopoulou S; Department of Physiology and Anatomy, University of North Texas Health Science Center at Fort Worth, TX, USA. Electronic address: styliani.goulopoulou@unthsc.edu.
Jazyk: angličtina
Zdroj: Pharmacological research [Pharmacol Res] 2021 Sep; Vol. 171, pp. 105788. Date of Electronic Publication: 2021 Jul 24.
DOI: 10.1016/j.phrs.2021.105788
Abstrakt: Uterine perivascular adipose tissue (PVAT) contributes to uterine blood flow regulation in pregnancy, at least in part, due to its effects on uterine artery reactivity. We tested the hypothesis that uterine PVAT modulates the balance between the contribution of nitric oxide synthase (NOS)- and cyclooxygenase (COX)-dependent pathways to acetylcholine (ACh)-induced relaxation in isolated uterine arteries. Concentration-response curves to ACh (1 nM - 30 µM) were performed on uterine arteries from pregnant and non-pregnant rats. Arteries were exposed to Krebs-Henseleit solution (control) or PVAT-conditioned media (PVATmedia) in the presence of the following inhibitors: L-NAME (NOS inhibitor), indomethacin (COX inhibitor), SC560 (COX-1 inhibitor), NS398 (COX-2 inhibitor), SQ 29,548 (thromboxane receptor (TP) inhibitor). In arteries incubated with PVATmedia, the presence of indomethacin increased ACh-induced relaxation, reversing the anti-dilatory effect of PVATmedia. NOS inhibition reduced ACh-induced relaxation in uterine arteries from pregnant rats, and exposure to PVATmedia did not change this effect. Selective inhibition of COX-1 but not COX-2 suppressed relaxation responses to ACh in control arteries. The presence of PVATmedia abolished the effect of COX-1 inhibition. Incubation of uterine arteries from pregnant rats with PVATmedia increased production of thromboxane B 2 (TxB 2 , p = 0.01) but thromboxane receptor (TP) inhibition did not affect the anti-dilatory properties of PVATmedia. In conclusion, inhibition of COX signaling suppressed the anti-dilatory effects of PVATmedia, while PVATmedia had no effect on the contribution of the NOS/NO pathway to ACh-induced relaxation in uterine arteries from pregnant rats, indicating that the anti-dilatory effects of uterine PVAT are mediated in part by COX-dependent mechanisms.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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