CLINICAL RESEARCH
Plasma Nitroso Compounds Are Decreased in Patients With Endothelial Dysfunction
Christian Heiss, MD*,
Thomas Lauer, MD ,
André Dejam, MD*,
Petra Kleinbongard, PhD*,
Sandra Hamada, MS*,
Tienush Rassaf, MD*,
Simone Matern, BS*,
Martin Feelisch, PhD and
Malte Kelm, MD*,*
* Department of Cardiology, Pneumology, and Vascular Medicine, RWTH Aachen, Aachen, Germany
Department of Cardiology, Pneumology, and Angiology, Heinrich-Heine University, Duesseldorf, Germany
Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts
Manuscript received May 5, 2005;
revised manuscript received June 3, 2005,
accepted June 27, 2005.
* Reprint requests and correspondence: Dr. Malte Kelm, Department of Cardiology, Pneumology, and Vascular Medicine, RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany (Email: mkelm{at}ukaachen.de).
OBJECTIVES: We investigated whether plasma nitros(yl)ated species (RXNOs) that mediate systemic nitric oxide (NO) bioactivity are depleted in individuals with cardiovascular risk factors and endothelial dysfunction.
BACKGROUND: Endothelium-derived NO acts not only as a regional messenger but exerts significant systemic effects via formation of circulating RXNOs delivering NO to sites of impaired production.
METHODS: Endothelial function was assessed in 68 patients with one to four major cardiovascular risk factors (RF) and 39 healthy control subjects (C) by measurement of flow-mediated dilation (FMD) of the brachial artery using high-resolution ultrasound. In parallel, plasma RXNOs were determined by reductive gas phase chemiluminescence.
RESULTS: Increasing numbers of risk factors were accompanied by a progressive decrease in FMD: 6.5 ± 0.4% (C); 4.7 ± 0.5% (one RF); 2.8 ± 0.4% (two RF); 2.2 ± 0.4% (three RF); and 1.0 ± 0.3% (four RF). Progressively impaired vascular function was associated with a concomitant decrease in plasma RXNOs (p < 0.01): 39 ± 2 nmol/l (C); 30 ± 2 nmol/l (one RF); 24 ± 3 nmol/l (two RF); 22 ± 3 nmol/l (three RF); and 15 ± 2 nmol/l (four RF), with univariate correlation between FMD and RXNO (r = 0.41, p < 0.001). In a multivariate regression model, RXNO was an independent predictor of endothelial function.
CONCLUSIONS: Endothelial dysfunction in patients with cardiovascular risk factors is associated with decreased levels of circulating RXNOs. Plasma RXNOs may be diagnostically useful markers of NO bioavailability and a surrogate index of endothelial function. Whether the observed decrease in concentration reflects impaired NO formation, accelerated decomposition, and/or consumption of RXNOs and whether these processes play a causal role in the pathophysiology of arteriosclerosis remain to be investigated.
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Abbreviations and Acronyms
| | BA = brachial artery | | eNOS = endothelial nitric oxide synthase | | FMD = flow-mediated dilation | | GTN = glycerol trinitrate | | NO = nitric oxide | | RXNO = sum of circulating nitric oxide species (synonym: circulating NO pool) |
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