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[Endothelial dysfunction in peripheral arterial occlusive disease: from basic research to clinical use]
1Institut für Klinische Pharmakologie, Medizinische Hochschule Hannover.
Abstract:
Nitric oxide (NO) exerts pleiotroptic anti-atherosclerotic effects in the vascular wall: vasodilation, inhibition of platelet aggregation, elukocyte adhesion, and smooth muscle cell proliferation. Experimental and clinical studies showed that the biological effects of NO are impaired in patients with peripheral arterial occlusive disease. In a cross over study with 77 PAOD patients, we could demonstrate impaired NO formation by measuring the index metabolites of NO, nitrate and cyclic GMP. One possible mechanism of these pathophysiological changes is accumulation of the endogenous inhibitor of NO synthesis, asymmetrical dimethylarginine (ADMA). The NO-mediated functions of the vascular endothelium will become increasingly important in the clinic: diagnostically, measuring endothelium-dependent vasodilation may become a risk indicator for the development or progression of cardiovascular disease and for assessing the effects of antiatherosclerotic therapy; therapeutically, treatment strategies will be developed aiming at improving endothelial function. In early clinical studies, administration of L-arginine, the amino acid precursor of endogenous NO, has resulted in increased NO formation rates, which may prove therapeutically effective in the future.
Insights
Patients with peripheral arterial occlusive disease (PAOD) show impaired nitric oxide (NO) formation. This may be due to increased asymmetrical dimethylarginine (ADMA), an inhibitor of NO synthesis, impacting vascular health.
Area of Science:
- Cardiovascular Science
- Vascular Biology
- Biochemistry
Background:
- Nitric oxide (NO) has multiple anti-atherosclerotic effects in the vascular wall, including vasodilation and inhibition of platelet aggregation.
- Biological functions of NO are often impaired in patients with peripheral arterial occlusive disease (PAOD).
Purpose of the Study:
- To investigate impaired NO formation in PAOD patients.
- To explore the role of asymmetrical dimethylarginine (ADMA) in the pathophysiology of PAOD.
- To highlight the clinical significance of NO-mediated endothelial functions.
Main Methods:
- Cross-over study involving 77 PAOD patients.
- Measurement of NO index metabolites: nitrate and cyclic guanosine monophosphate (cGMP).
- Assessment of asymmetrical dimethylarginine (ADMA) levels.
Main Results:
- Demonstrated impaired NO formation in PAOD patients.
- Identified potential link between ADMA accumulation and impaired NO synthesis.
- Indicated that endothelial NO functions are crucial for cardiovascular disease risk assessment and therapeutic strategies.
Conclusions:
- Impaired NO formation is a feature of PAOD, potentially linked to elevated ADMA.
- Endothelium-dependent vasodilation measurement could serve as a diagnostic risk indicator.
- Therapeutic strategies targeting endothelial function, such as L-arginine administration, show future promise.