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Relevance of the NOS3 T–786C and G894T variants for cholinergic and adrenergic coronary vasomotor responses in man

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Abstract

Objective

We investigated the impact of the –786C allele at the promoter and the 894T allele in exon 7 of the gene encoding the endothelial nitric oxide synthase (NOS3) on coronary vasomotor responses to exogenous and endogenous stimuli.

Methods

In 47 individuals undergoing coronary angiography for chest pain, but without significant stenosis in the left anterior descending artery (LAD), nitroglycerine and acetylcholine were infused intracoronarily, and a cold pressor test (CPT) was performed. Coronary blood flow (CBF) in the LAD was calculated from quantitative coronary angiography and intracoronary Doppler measurements. Aortic and coronary sinus lactate levels were determined in 18 individuals. To analyze the impact of NOS3 genotypes, a logistic regression model was used.

Results

In response to acetylcholine (p = 0.002) and CPT (p = 0.015) CBF reduction was associated with homocygosity for the –786C allele. Myocardial lactate uptake was reversed into net lactate production in CC homocygotes. No independent effects of the G894T polymorphism were observed in the present study. Haplotype analysis revealed a significant linkage disequilibrium between both polymorphisms (p < 0.001).

Conclusions

Our findings suggest a pathophysiologically relevant role for the T–786C polymorphism in human coronary vasomotion. The observed linkage disequilibrium between both NOS3 genotypes deserves further research in future studies.

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Authors and Affiliations

  1. Klinik für Kardiologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    Ch. K. Naber M.D., O. Oldenburg, K. Brauck, H. Eggebrecht, A. Schmermund, D. Baumgart & R. Erbel

  2. Institut für Pharmakologie und Toxikologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    U. H. Frey & W. Siffert

  3. Institut für Pathophysiologie Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstr. 55, 45122, Essen, Germany

    G. Heusch

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  1. Ch. K. Naber M.D.
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  2. U. H. Frey
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  3. O. Oldenburg
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  4. K. Brauck
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  5. H. Eggebrecht
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  6. A. Schmermund
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  7. D. Baumgart
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  8. R. Erbel
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  9. W. Siffert
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  10. G. Heusch
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Correspondence to Ch. K. Naber M.D..

Additional information

Prof. Dr. M. Kelm, Düsseldorf, Germany, served as guest editor for the manuscript and was responsible for all editorial decisions, including the selection of reviewers. This policy applies to all manuscripts with authors from the editor’s institution.

Drs. Naber and Frey contributed equally to this manuscript

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Naber, C.K., Frey, U.H., Oldenburg, O. et al. Relevance of the NOS3 T–786C and G894T variants for cholinergic and adrenergic coronary vasomotor responses in man. Basic Res Cardiol 100, 453–460 (2005). https://doi.org/10.1007/s00395-005-0530-y

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  • DOI: https://doi.org/10.1007/s00395-005-0530-y

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