Faculty Collaboration Database

Novel mechanism of vasodilation in inflammatory bowel disease. Arterioscler Thromb Vasc Biol 2005 Nov;25(11):2355-61

Date

09/06/2005

Pubmed ID

16141408

DOI

10.1161/01.ATV.0000184757.50141.8d

Scopus ID

2-s2.0-27644598991 (requires institutional sign-in at Scopus site)   25 Citations

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.

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.

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.

Author List

Hatoum OA, Gauthier KM, Binion DG, Miura H, Telford G, Otterson MF, Campbell WB, Gutterman DD

Authors

William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Mary F. Otterson MD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Acetylcholine
Adult
Aged
Arachidonic Acid
Arterioles
Biological Factors
Carbon Radioisotopes
Cyclooxygenase Inhibitors
Endothelium, Vascular
Female
Humans
In Vitro Techniques
Indomethacin
Inflammatory Bowel Diseases
Male
Microscopy, Video
Middle Aged
Nitric Oxide
Prostaglandin D2
Reactive Oxygen Species
Receptors, Immunologic
Receptors, Prostaglandin
Vasodilation
Vasodilator Agents