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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Chronic cyclooxygenase-2 inhibition prevents the worsening of hypertension and endothelial dysfunction induced by ouabain in resistance arteries of spontaneously hypertensive rats

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Author(s):
de Oliveira, Helane Tito [1] ; Couto, Gisele Kruger [1] ; Davel, Ana Paula [2] ; Xavier, Fabiano Elias [3] ; Rossoni, Luciana Venturini [1]
Total Authors: 5
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Prof Lineu Prestes Av, Rm 225, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Estadual Campinas, Dept Struct & Funct Biol, Campinas - Brazil
[3] Univ Fed Pernambuco, Biosci Ctr, Dept Physiol & Pharmacol, Recife, PE - Brazil
Total Affiliations: 3
Document type: Journal article
Source: VASCULAR PHARMACOLOGY; v. 139, AUG 2021.
Web of Science Citations: 0
Abstract

Aim: Previous studies raise cyclooxygenase (COX) activation as a possible mechanism involved in the pathophysiology of ouabain-induced hypertension. We hypothesized that inhibition of COX-2 activity might prevent ouabain-induced vascular dysfunction and worsening of hypertension in spontaneously hypertensive rats (SHR). Methods: SHR were exposed to ouabain or vehicle and treated or not with the selective COX-2 inhibitor nimesulide for 5 weeks. Systolic blood pressure was measured by plethysmography. Vascular reactivity by wire myograph and protein expression by Western-blot were assessed in mesenteric resistance arteries (MRA) of groups. Thromboxane A2 (TXA2) production by ELISA was evaluated in MRA supernatants of groups. Results: Noradrenaline-induced maximal contraction (Emax) was greater in MRA from SHR receiving ouabain than those of vehicle group. In situ inhibition of COX-2, TXA2 synthase, or TP receptor reduced the Emax to noradrenaline in MRA of ouabain to vehicle levels. TXA2 production was higher in ouabain than in vehicle group. Ouabain enhanced expression of cytoplasmic tyrosine kinase Src (c-Src)/ERK1/2/COX-2/TXA2 synthase/TP receptor in SHR MRA, but did not change NFkB/iKB ratio. Anticontractile effect of nitric oxide (NO) was smaller in MRA from ouabain- than vehicle-treated SHR, as well as eNOS and nNOS expression. Nimesulide co-treatment prevented the ouabain-induced worsening of hypertension and noradrenaline MRA hypercontractility in SHR. Conclusion: Ouabain worsen hypertension and induce MRA hypercontractility in SHR associated with upregulated c-Src/ERK1/2/COX-2/TXA2 synthase/TXA2/TP receptor axis. These effects were prevented by COX-2 inhibition. (AU)

FAPESP's process: 10/18380-6 - Role of endogenous ouabain on vascular function and autonomic modulation in DOCA-Salt hypertensive rats
Grantee:Luciana Venturini Rossoni
Support Opportunities: Regular Research Grants