Endothelial Dysfunction of Coronary Resistance Arteries Is Improved by Tetrahydrobiopterin in Atherosclerosis
| Autor: | Achim M. Vogt, Wolfgang Kübler, Christiane P. Tiefenbacher, Christian F. Vahl, Kerstin Amann, Tina Bleeke |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Nitroprusside
Serotonin medicine.medical_specialty Endothelium Arteriosclerosis Vasodilator Agents Ischemia Hemodynamics In Vitro Techniques Substance P Nitric oxide chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Humans Atrial Appendage Endothelial dysfunction Dose-Response Relationship Drug Vascular disease business.industry Pteridines Tetrahydrobiopterin medicine.disease Biopterin Coronary Vessels Acetylcholine Pathophysiology Pterins Vasodilation Cholesterol Endocrinology medicine.anatomical_structure chemistry Vasoconstriction cardiovascular system Diet Atherogenic Swine Miniature Vascular Resistance Endothelium Vascular Cardiology and Cardiovascular Medicine business Histamine medicine.drug |
| Zdroj: | Circulation. 102:2172-2179 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.102.18.2172 |
| Popis: | Background —Tetrahydrobiopterin (BH4), an essential cofactor for the synthesis of NO, improves endothelial dysfunction after ischemia/reperfusion. Therefore, we hypothesized that reduction of BH4 is involved in the attenuation of endothelium-dependent vasodilation in atherosclerosis, and we investigated the effect of alterations of the BH4 level on the vasodilatory potential of coronary resistance vessels from humans and pigs with atherosclerosis. Methods and Results —Coronary arterioles were obtained from patients undergoing CABG (atherosclerosis group) or valve replacement (control group) and from pigs fed either a standard diet (control group) or atherogenic diet (atherosclerosis group). After isolation, vessels were cannulated, pressurized, and placed on the stage of an inverted microscope. Dose-response curves were investigated in response to the endothelium-dependent agonists histamine, serotonin, and acetylcholine (for pigs, substance P) and to the endothelium-independent agonist sodium nitroprusside (SNP) under control conditions and before and after incubation of the vessels with sepiapterin (substrate for BH4 synthesis). In vessels from patients and from animals with atherosclerosis, compared with vessels from the control groups, there was a significant ( P Conclusions —Atherosclerosis severely compromises endothelial function of coronary resistance arteries. Administration of sepiapterin leads to a significant improvement of endothelium-dependent vasodilatation to different agonists in vessels from humans and pigs with atherosclerosis. Therefore, we conclude that a reduced availability of BH4 is involved in the development of endothelial dysfunction in atherosclerosis. |
| Databáze: | OpenAIRE |
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