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Copyright (c) 2025 Muhammed Ahmed-Reda Elosman, Sefika Pinar Senol, Elif Ikiz, Bahar Tunctan
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Urotensin-II receptor contributes to the pro-inflammatory TLR4/MyD88/NF-κB/iNOS/NO pathway-mediated cardiovascular response to systemic lipopolysaccharide challenge in a septic shock model in rats
Corresponding Author(s) : Bahar Tunctan
Cellular and Molecular Biology,
Vol. 71 No. 5: Issue 5
Abstract
Urotensin (U)-II through the U-II receptor (UT) (the orphan G protein-coupled receptor; GPR14) plays an important role in the pathogenesis of many cardiovascular and renal diseases characterized by increased production of vasodilatory and pro-inflammatory mediators. This study tested the hypothesis of whether UT contributes to the pro-inflammatory TLR4/MyD88/NF-kB/iNOS/NO pathway-mediated changes in the cardiovascular response to systemic lipopolysaccharide (LPS) challenge in a rat model of septic shock. SB-710411, a UT antagonist, was used to test this hypothesis. Rats were injected with SB-710411 1 hour following an injection of saline or LPS. A tail-cuff device was used to record the mean arterial pressure and heart rate values of rats. Serum U-II and nitrite levels and U-II, GPR14, TLR4, MyD88, NF-kB, IL-1β, and iNOS mRNA expression in the cardiovascular and renal tissues were measured. Mean arterial pressure was reduced and heart rate was increased at 4 hours following LPS injection. In addition to the levels of U-II and nitrite in the sera of rats injected with LPS, the expression of U-II, GPR14, TLR4, MyD88, NF-kB, IL-1β, and iNOS was increased in the cardiovascular and renal tissues. SB-710411 at 0.01 mg/kg dose ameliorated the changes induced by LPS, excepting the increased serum nitrite level. These findings suggest that UT contributes to hypotension and tachycardia mediated by the TLR4/MyD88/NF-kB/iNOS/NO pathway, accompanied by an increase in pro-inflammatory cytokine expression in tissues related to the cardiovascular and renal systems, in response to systemic LPS challenge in rats.
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