Mechanisms underlying sodium nitroprusside-induced tolerance in the mouse aorta: Role of ROS and cyclooxygenase-derived prostanoids

Author(s)

Diniz, Mariana C. ; Olivon, Vania C. ; Tavares, Livia D. ; Simplicio, Janaina A. ; Gonzaga, Natalia A. ; de Souza, Daniele G. ; Bendhack, Lusiane M. ; Tirapelli, Carlos R. ; Bonaventura, Daniella

• Document type: Journal article
• Source: Life Sciences; v. 176, p. 26-34, MAY 1 2017.
• Web of Science Citations: 3

Abstract

Aims: To determine the role of reactive oxygen species (ROS) on sodium nitroprusside (SNP)-induced tolerance. Additionally, we evaluated the role of ROS on NF-kappa B activation and pro-inflammatory cytokines production during SNP-induced tolerance. Main methods: To induce in vitro tolerance, endothelium-intact or -denuded aortic rings isolated from male Balb-c mice were incubated for 15, 30, 45 or 60 min with SNP (10 nmol/L). Key findings: Tolerance to SNP was observed after incubation of endothelium-denuded, but not endothelium intact aortas for 60 min with this inorganic nitrate. Pre-incubation of denuded rings with tiron (superoxide anion (O-2(-)) scavenger), and the NADPH oxidase inhibitors apocynin and atorvastatin reversed SNP-induced tolerance. L-NAME (non-selective NOS inhibitor) and L-arginine (NOS substrate) also prevented SNP-induced tolerance. Similarly, ibuprofen (non-selective cyclooxygenase (COX) inhibitor), nimesulide (selective COX-2 inhibitor), AH6809 (prostaglandin PGF(2)alpha receptor antagonist) or SQ29584 {[}PGH(2)/thromboxane TXA(2) receptor antagonist] reversed SNP-induced tolerance. Increased ROS generation was detected in tolerant arteries and both tiron and atorvastatin reversed this response. Tiron prevented tolerance-induced increase on O-2(-) and hydrogen peroxide (H2O2) levels. The increase onp65/NF-kappa B expression and TNF-alpha production in tolerant arteries was prevented by tiron. The major new finding of our study is that SNP-induced tolerance is mediated by NADPH-oxidase derived ROS and vasoconstrictor prostanoids derived from COX-2, which are capable of reducing the vasorelaxation induced by SNP. Additionally, we found that ROS mediate the activation of NF-kappa B and the production of TNF-alpha in tolerant arteries. Significance: These findings identify putative molecular mechanisms whereby SNP induces tolerance in the vasculature. (C) 2017 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 09/17607-0 - Nitric oxide donors, nitrite and nonsteroidal antiinflammatory agents combined with nitric oxide
• Grantee: Lusiane Maria Bendhack
• Support Opportunities: Regular Research Grants