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Novel mechanism of vasodilation in inflammatory bowel disease.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2005 Nov; Vol. 25 (11), pp. 2355-61. Date of Electronic Publication: 2005 Sep 01. - Publication Year :
- 2005
-
Abstract
- Objective: Endothelium-dependent dilation to acetylcholine (Ach) is reduced in mucosal arterioles from patients with inflammatory bowel disease (IBD). The contributions of both nitric oxide (NO) and endothelial-derived hyperpolarizing factor (EDHF) are decreased. We hypothesized that the remaining dilation results from products of cyclooxygenase.<br />Methods and Results: High-performance liquid chromatography (HPLC) was used to isolate eicosanoid vasodilator products and videomicroscopy was used to examine vasomotor responses in human mucosal arterioles from subjects with or without IBD undergoing bowel resection surgeries. In subjects without IBD, Ach constricted (-52%+/-10%) arterioles devoid of endothelium. Indomethacin (INDO) (cyclooxygenase inhibitor) had no effect. In contrast, Ach dose-dependently dilated both intact and endothelial denuded arterioles from patients with IBD. The dilation was converted to constriction by INDO (-54%+/-9%; P<0.05 versus non-IBD) or by BWA868C (PGD2 receptor antagonist). Only in arterioles from subjects with IBD did Ach produce an arachidonic acid metabolite that comigrated on HPLC with PG D2 (PGD2). Exogenous PGD2 dilated (max=66%+/-4%) IBD arterioles.<br />Conclusions: In arterioles from IBD patients, Ach-mediated dilation shifts from endothelial production of NO and EDHF to nonendothelial generation of a PG, likely PGD2. This is a novel dilator mechanism arising from nonendothelial vascular tissue that compensates for loss of endothelium-dependent dilation. PGD2 appears to be important in regulating mucosal blood flow in patients with IBD, implicating potentially detrimental effects from nonsteroidal antiinflammatory drugs.
- Subjects :
- Acetylcholine pharmacology
Adult
Aged
Arachidonic Acid pharmacokinetics
Biological Factors metabolism
Carbon Radioisotopes
Cyclooxygenase Inhibitors pharmacology
Endothelium, Vascular metabolism
Female
Humans
In Vitro Techniques
Indomethacin pharmacology
Male
Microscopy, Video
Middle Aged
Nitric Oxide metabolism
Prostaglandin D2 metabolism
Reactive Oxygen Species metabolism
Receptors, Immunologic antagonists & inhibitors
Receptors, Immunologic metabolism
Receptors, Prostaglandin antagonists & inhibitors
Receptors, Prostaglandin metabolism
Vasodilation drug effects
Vasodilator Agents pharmacology
Arterioles physiology
Inflammatory Bowel Diseases metabolism
Inflammatory Bowel Diseases physiopathology
Vasodilation physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 25
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16141408
- Full Text :
- https://doi.org/10.1161/01.ATV.0000184757.50141.8d