Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in dogs in vivo.

Abstract

Studies in vitro suggested that inflammatory cytokines could cause myocardial dysfunction. However, the detailed mechanism for the cytokine-induced myocardial dysfunction in vivo remains to be examined. We thus examined this point in our new canine model in vivo, in which microspheres with and without IL-1 ␤ were injected into the left main coronary artery. Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 wk. Immediately after the microsphere injection, LVEF decreased to ‫ف‬ 30% in both groups. While LVEF rapidly normalized in 2 d in the control group, it was markedly impaired in the IL-1 ␤ group even at day 7. Pretreatment with dexamethasone or with aminoguanidine, an inhibitor of inducible nitric oxide synthase, prevented the IL-1 ␤ -induced myocardial dysfunction. Nitrotyrosine concentration, an in vivo marker of the peroxynitrite production by nitric oxide and superoxide anion, was significantly higher in the myocardium of the IL-1 ␤ group than in that of the control group or the group cotreated with dexamethasone or aminoguani-

Repetitive hyperthermia attenuates progression of left ventricular hypertrophy and increases telomerase activity in hypertensive rats

“…Evidence from experimental models of heart failure show that oxidative stress is increased in the failing heart and contributes to the pathophysiology of heart failure (5). iNOS, oxidative stress, and nitrotyrosine, which is the footprint of peroxynitrite, were induced by inflammation caused by heart failure (23).…”

Cytokine-Induced Modulation of Cardiac Function

“…16,17 These observations were extended by studies in rats demonstrating that sustained infusion of TNF-␣ caused time-dependent contractile dysfunction and LV dilatation that was partially reversed by stopping the infusion or on concomitant treatment with a TNF-␣ antagonist, 18 and studies in dogs showing that intracoronary injection of IL-1␤ coated microspheres induced sustained LV dysfunction. 19 This concept was subsequently confirmed by the observation that cardiac-specific TNF-␣ overexpression in mice induced LV dilatation, reduced ejection fraction, depressed catecholamine responsiveness, and premature mortality. 20 Several studies have specifically evaluated the in vivo effects of cytokines on cardiac function, often using TNF-␣ as a prototypic proinflammatory cytokine (Table 1).…”

Protein nitration is mediated by heme and free metals through Fenton-type chemistry: An alternative to the NO/O\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy}\usepackage{mathrsfs}\setlength{\oddsidemargin}{-69pt}\begin{document}\begin{equation*}{\mathrm{_{2}^{-}}}\end{equation*}\end{document} reaction

“…N itrated tyrosine residues (NT) have been used as a marker of the involvement of nitric oxide (NO) and its related chemistry in a number of pathophysiological disorders including cardiovascular (1, 2) neurodegenerative and malignant conditions (1)(2)(3)(4)(5), such as septic shock (6), multiple sclerosis (7), Alzheimer's disease (8), and amyotrophic lateral sclerosis (9). In cancer the presence of NT often correlates with a poor prognosis (10), suggesting diagnostic implications.…”