| Endothelial dysfunction of coronary resistance vessels in apoE-/- mice involves NO but not prostacyclin-dependent mechanisms. | |
| | |
MedLine Citation:
|
PMID: 11744035 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
OBJECTIVE: We have analyzed the extent of endothelial dysfunction in cardiac resistance vessels of hyperlipidaemic apoE-/- mice and explored whether NO and/or prostacyclin dependent pathways are involved. METHODS: Coronary resistance was measured in isolated perfused hearts from WT and apoE-/- mice. To discriminate between NO and PGI(2)-dependent flow responses, we made use of the finding that acetylcholine (ACh) predominantly activates the prostaglandin pathway whereas bradykinin (Bk) mainly acts via NO in murine cardiac resistance vessels. RESULTS: Basal coronary flow as well as the ACh induced vasodilation (0.1-1 microM) were not different between WT and apoE-/- hearts (flow increase+100%). Similarly, vasodilation in response to the prostacyclin mimetic iloprost reached the same levels. In contrast, the Bk-stimulated [3.3 microM Bk] coronary flow was reduced from 31.6+/-4.2 in WT to 19.2+/-2.7 ml min(-1) g(-1) in apoE-/- hearts. NOS inhibition by ethylisothiourea (ETU, 10 microM) reduced basal as well as Bk-stimulated coronary flow in WT and apoE-/- hearts to the same extent. RT-PCR and Western analysis demonstrated that neither eNOS expression nor protein levels were reduced. Similarly, the flow response to the NO donor SNAP (0.3-33 microM) was not altered suggesting that soluble guanylyl cyclase was not affected. Intracoronary application of superoxide dismutase augmented the Bk-induced vasodilation of apoE-/- hearts almost back to WT levels (26.6+/-3.3 ml min(-1) g(-1)). In line with this finding the NADPH induced O(2)(-) formation was enhanced in cardiac extracts from apoE-/- hearts. CONCLUSION: apoE-/- hearts develop a hemodynamically relevant endothelial dysfunction at the level of coronary resistance vessels most likely via inactivation of bioavailable NO by superoxide anions. The function of the prostacyclin system is not altered. |
| | |
Authors:
|
Axel Gödecke; Martin Ziegler; Zhaoping Ding; Jürgen Schrader |
Related Documents
:
|
22226005 - The high-risk myocardial infarction database initiative. 16043025 - Evidence of cardiovascular protection by moderate alcohol: role of nitric oxide. 2881635 - Long-term nitroglycerin treatment: effect on direct and endothelium-mediated large coro... 7181835 - Effects of heart rate on hemodynamic severity of coronary artery stenosis in the dog. 8034865 - Influence of residual perfusion within the infarct zone on the natural history of left ... 19407085 - Clinical findings and serum cardiac troponin i concentrations in horses after intragast... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cardiovascular research Volume: 53 ISSN: 0008-6363 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2002 Jan |
Date Detail:
|
Created Date: 2001-12-17 Completed Date: 2002-05-30 Revised Date: 2006-11-15 |
Medline Journal Info:
|
Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: Netherlands |
Other Details:
|
Languages: eng Pagination: 253-62 Citation Subset: IM |
Affiliation:
|
Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Postfach 101007, 40001 Düsseldorf, Germany. axel.goedecke@uni-duesseldorf.de |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Acetylcholine
/
pharmacology Adenosine / pharmacology Analysis of Variance Animals Apolipoproteins E / genetics, physiology* Bradykinin / pharmacology Cholesterol, LDL / blood Coronary Vessels Cyclooxygenase Inhibitors / pharmacology Diclofenac / pharmacology Dose-Response Relationship, Drug Endothelium, Vascular / metabolism* Enzyme Inhibitors / pharmacology Epoprostenol / metabolism* Hypercholesterolemia / genetics, metabolism* Iloprost / pharmacology Mice Mice, Inbred C57BL Mice, Mutant Strains Nitric Oxide / metabolism* Nitric Oxide Synthase / antagonists & inhibitors Perfusion Superoxide Dismutase / pharmacology Vascular Resistance / drug effects Vasodilator Agents / pharmacology omega-N-Methylarginine / pharmacology |
| Chemical | |
Reg. No./Substance:
|
0/Apolipoproteins E; 0/Cholesterol, LDL; 0/Cyclooxygenase Inhibitors; 0/Enzyme Inhibitors; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 15307-86-5/Diclofenac; 17035-90-4/omega-N-Methylarginine; 35121-78-9/Epoprostenol; 51-84-3/Acetylcholine; 58-61-7/Adenosine; 58-82-2/Bradykinin; 78919-13-8/Iloprost; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.15.1.1/Superoxide Dismutase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Mechanisms underlying maintenance of smooth muscle cell quiescence in rat aorta: role of the cyclin ...
Next Document: Cardiovascular response to acute hypoxemia in adult rats hypoxemic neonatally.