Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries

Aoki, Nobuo; Siegfried, Martin R.; Lefer, Allan M.

doi:10.1152/ajpheart.1989.256.5.h1509

Cited by 78 publications

(47 citation statements)

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“…However, as we found that the endothelium played a protective role and was not the primary mediator of the harmful effect of LPS-activated macrophages, the L-arginine pathway ofthe endothelium was unlikely to have been involved in contractility depression. This is corroborated by in vitro studies showing that LPS and monokines reduce EDRF release (47,52,53). In the present work, similar protection against LPS-activated macrophages was observed in both deendothelialized and intact arteries exposed extraluminally to LNMMA.…”

Section: Discussionsupporting

confidence: 90%

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Bernard

Szekély²,

Philip³

et al. 1992

J. Clin. Invest.

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Inflammatory mediators released by macrophages (M+) are believed to be involved in septic vasoplegia. To investigate the effect of My on vascular reactivity, excised rabbit carotids were exposed intraluminally either to peritoneal rabbit ME, activated by 18 h of incubation with 1 gg/ml lipopolysaccharide, or to the supernatants (SPN) derived from them. The contractile responses to phenylephrine (PE, 10-6 M) were determined by measuring changes in diameter using an ultrasonic microdimensiometer 1, 2, and 3 h after the first control contraction. In control arteries (n = 12), PE-induced contractions were, respectively, 102.9±3.3%, 95.2±4.1%, and 89.7±3.8% of the first contraction, after 1, 2, and 3 h. Activated M4 significantly reduced PE-stimulated contractions after as little as 1 h of carotid exposure (percentage of controls at 1, 2, or 3 h: 74.1±5.6, 57.2±5.2, and 34.2±5.6, n = 10, P < 0.001). The activated macrophage-derived SPN took longer to diminish carotid contractility than the Mt themselves, and became significant only after 2 h. The greater effect of Mt might be due to cooperation between Mt and vascular cells, as suggested by the amplified interleukin-1 release observed after Mt infusion. The presence of the endothelium partially protected carotid contractility from depression by activated Mt. Extraluminal addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis prevented this depression in arteries with or without endothelium. No products of the oxidative pathway of L-arginine were detected in rabbit activated Mt. These results suggest that activation of this pathway in smooth muscle cells seems to be involved in vascular hypocontractility. (J. Clin.

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Section: Discussionsupporting

confidence: 90%

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Bernard

Szekély²,

Philip³

et al. 1992

J. Clin. Invest.

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“…Sci. USA 90 (1993) endothelium-derived nitric oxide (24,25). The significance of preserving nitric oxide extends far beyond maintaining the ability ofthe vasculature to dilate, since endothelium-derived nitric oxide also exerts anti-aggregation actions in platelets (26) and anti-adherence effects in neutrophils (27) and quenches superoxide radicals (28).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of the cardioprotective effect of transforming growth factor beta 1 in feline myocardial ischemia and reperfusion.

Lefer

Liang

Weyrich

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

105

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We studied the effects of transforming growth factor Pi (TGF-f1) in a feline model of myocardial ischemia (1.5 hr) and reperfusion (4.5 hr). Myocardial ischenma followed by reperfusion resulted in severe myocardial imjury, endothelial dysfunction, high cardiac myeloperoxidase activity indicative of neutrophil accumulation in the ischemic myocardium, and sinicant neutrophil adherence to the ischemic coronary endothelium. In contrast, intravenous administration of TGF-Pi (20 pg/kg) 30 min prior to reperfusion significantly attenuated myocardial necrosis (13.8% ± 3.5% vs. 32.2% ± 2.9% of area-at-risk, P < 0.01) and attenuated endothelial dysfunction (P < 0.01) associated with ischemia- Experimental Protocol. After completing all surgical procedures, the cats were allowed to stabilize for 30 min, at which time a baseline reading of ECG and MABP was recorded and a 3-ml blood sample was drawn. The blood was centrifuged at 2500 x g for 15 min at 4°C to obtain plasma that was used as a vehicle for TGF-,Bl administration. MI was produced by tightening the previously placed reversible ligature around the LAD coronary segment to completely occlude the vessel. This was designated as time 0. One hour after coronary occlusion, 81 (20 ,ug/kg) or its vehicle (1 ml of plasma) was given i.v. as a bolus. After 1.5 hr of ischemia, the LAD ligature was untied and the ischemic myocardium was reperfused (R) for 4.5 hr. The animals were randomly divided into three major groups of six or seven cats each. These groups included sham MI + R cats receiving TGF-f31 and MI + R cats receiving either TGF-(31 or its vehicle. Sham MI + R cats were subjected to the same surgical procedures as MI + R cats except that the LAD coronary artery was not occluded.Myocardial Tissue Analysis. At the end of the experiment, the ligature around the LAD coronary segment was retightened. Twenty milliliters of0.5% Evans blue was injected over a period of 1 min into the left ventricle to stain the area of Abbreviations: TGF-(, transforming growth factor (; MABP, mean arterial blood pressure; LAD, left anterior descending; PRI, pressure-rate index; HR, heart rate; MI, myocardial ischemia; ACh, acetylcholine; MPO, myeloperoxidase; PMN, polymorphonuclear leukocyte; IL-1, interleukin 1; TNF-a, tumor necrosis factor a; LCX, left circumflex; ECG, electrocardiogram; LTB4, leukotriene B4; EDRF, endothelium-derived relaxing factor. tTo whom reprint requests should be addressed. 1018The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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“…51,52 In the setting of atherosclerosis in which steady-state eNOS mRNA has been shown to be downregulated, 9,10 the contribution of TNF-␣ may be crucial to the pathogenesis of the disease. Some of the earliest published studies of eNOS gene regulation identified modulation of mRNA stability as a regulatory target of pro-inflammatory cytokines.…”

Section: Tnf-␣ and Lipopolysaccharidementioning

confidence: 99%

Endothelial Nitric Oxide Synthase

Tai

Robb

Marsden

2004

ATVB

137

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Abstract-Advances in our understanding of the molecular mechanisms involved in the constitutive and regulated expression of endothelial nitric oxide synthase (eNOS) mRNA expression present a new level of complexity to the study of endothelial gene regulation in health and disease. Recent studies highlight the contribution of both transcription and RNA stability to net steady-state mRNA levels of eNOS in vascular endothelium, introducing a new paradigm to gene regulation in the injured blood vessel. Constitutive eNOS expression is dependent on basal transcription machinery in the core promoter, involving positive and negative protein-protein and protein-DNA interactions. Chromatin-based mechanisms and epigenetic events also regulate expression of eNOS at the transcriptional level in a cell-restricted fashion. Although constitutively active, important physiological and pathophysiologic stimuli alter eNOS gene transcription rates. For instance, eNOS transcription rates increase in response to lysophosphatidylcholine, shear stress, and TGF-␤, among others. Under basal conditions, eNOS mRNA is extremely stable. Surprisingly, posttranscriptional mechanisms have emerged as important regulatory pathways in the observed decreases in eNOS expression in some settings. In models of inflammation, proliferation/injury, oxidized low-density lipoprotein treatment, and hypoxia, eNOS mRNA destabilization plays a significant role in the rapid downregulation of eNOS mRNA levels.

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Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries

Cited by 78 publications

References 0 publications

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Activated macrophages depress the contractility of rabbit carotids via an L-arginine/nitric oxide-dependent effector mechanism. Connection with amplified cytokine release.

Mechanism of the cardioprotective effect of transforming growth factor beta 1 in feline myocardial ischemia and reperfusion.

Endothelial Nitric Oxide Synthase

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