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Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors

Division of Nephrology and Hypertension, Department of Medicine, Georgetown University, Washington, DC 20007, USA
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Antioxidants 2019, 8(6), 193; https://doi.org/10.3390/antiox8060193
Received: 21 March 2019 / Revised: 12 June 2019 / Accepted: 19 June 2019 / Published: 22 June 2019
(This article belongs to the Special Issue Oxidative Stress Biomarkers in Cardiovascular Risk and Disease)
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Abstract

(1) Background: Angiotensin II (Ang II) and endothelin 1 (ET-1) generate reactive oxygen species (ROS) that can activate cyclooxygenase (COX). However, thromboxane prostanoid receptors (TPRs) are required to increase systemic markers of ROS during Ang II infusion in mice. We hypothesized that COX and TPRs are upstream requirements for the generation of vascular ROS by ET-1. (2) Methods: ET-1-induced vascular contractions and ROS were assessed in mesenteric arterioles from wild type (+/+) and knockout (−/−) of COX1 or TPR mice infused with Ang II (400 ng/kg/min × 14 days) or a vehicle. (3) Results: Ang II infusion appeared to increase microvascular protein expression of endothelin type A receptors (ETARs), TPRs, and COX1 and 2 in COX1 and TPR +/+ mice but not in −/− mice. Ang II infusion increased ET-1-induced vascular contractions and ROS, which were prevented by a blockade of COX1 and 2 in TPR −/− mice. ET-1 increased the activity of aortic nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and decreased superoxide dismutase (SOD) 1, 2, and 3 in Ang-II-infused mice, which were prevented by a blockade of TPRs. (4) Conclusion: Activation of vascular TPRs by COX products are required for ET-1 to increase vascular contractions and ROS generation from NADPH oxidase and reduce ROS metabolism by SOD. These effects require an increase in these systems by prior infusion of Ang II. View Full-Text
Keywords: endothelin 1 (ET-1); reactive oxygen species (ROS); cyclooxygenase (COX); thromboxane prostanoid receptors (TPRs); micro-resistant vessels; superoxide dismutase (SOD); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; tempol endothelin 1 (ET-1); reactive oxygen species (ROS); cyclooxygenase (COX); thromboxane prostanoid receptors (TPRs); micro-resistant vessels; superoxide dismutase (SOD); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; tempol
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MDPI and ACS Style

Wilcox, C.S.; Wang, C.; Wang, D. Endothelin-1-Induced Microvascular ROS and Contractility in Angiotensin-II-Infused Mice Depend on COX and TP Receptors. Antioxidants 2019, 8, 193.

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