Cyclooxygenase-1-sensitive oxidative responses to thromboxane-prostanoid receptor activation during vascular aging and experimental menopause.

Authors

Xavier Vidal-Gómez, Gloria Segarra, Ana Paula Dantas, Carlos Hermenegildo, Susana Novella, Pascual Medina

Published in

Biochemical pharmacology. Pages 118521. Oct 03, 2026. Epub Oct 03, 2026.

Abstract

Vascular aging and menopause increase cardiovascular risk in females, but the interplay among cyclooxygenase-1 (COX-1), thromboxane-prostanoid (TP) receptor signaling, nitric oxide (NO), and oxidative stress in the aging female vasculature remains unclear. We examined TP receptor-mediated responses in thoracic aortas from senescence-accelerated mouse-resistant 1 (SAMR1) and senescence-accelerated mouse-prone 8 (SAMP8) mice subjected to sham surgery (Sham), ovariectomy (Ovx), or ovariectomy followed by estradiol replacement (OvE). Aortic rings were exposed to U46619 (10^-9-3x10^-7 M) before and after incubation with the COX-1 inhibitor SC-560 (10^-7 M), the nitric oxide synthase (NOS) inhibitor N^G-nitro-L‑arginine methyl ester (L-NAME, 10^-4 M), or both. Superoxide production was assessed by dihydroethidium (DHE) fluorescence after exposure to U46619 (10^-8 M), with or without SC-560, and COX-1 expression was evaluated. U46619 induced concentration-dependent contractions in both strains. In Sham and OvE mice, L-NAME enhanced TP receptor-mediated contraction, whereas SC-560 exerted little effect. This L-NAME effect was blunted after ovariectomy; however, combined NOS and COX-1 inhibition significantly increased contractile responses. Ovariectomized SAMP8 mice showed the greatest TP receptor-mediated contractions, whereas estradiol replacement reduced contractile responses and restored NO-dependent modulation. U46619 increased vascular DHE fluorescence in all groups, and SC-560 attenuated this response. However, after ovariectomy, fluorescence remained significantly above basal levels despite COX-1 inhibition. COX-1 gene expression showed no major strain- or hormone-dependent differences. These findings indicate that estrogen status shapes TP receptor-mediated vascular responses by modulating NO-dependent restraint and reveal a COX-1-sensitive component of TP receptor-associated oxidative signaling in the absence of major changes in vascular COX-1 expression.

PMID:
42829113
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

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