Acute coronary artery injury in dogs following administration of CI-1034, an endothelin A receptor antagonist.

Abstract:

:The objective of this study was to characterize acute coronary artery injury evoked by the endothelin A receptor (ETAR) antagonist, CI-1034. Male dogs (n = 5) were intravenously administered CI-1034 at 120 mg/kg for 4 d. Control animals (n = 3) received vehicle. Macroscopically, drug-related hemorrhage was observed in the right coronary groove and atrium. Histologically, drugrelated coronary changes were characterized as medial hemorrhage and necrosis, with mixed inflammatory-cell infiltrates in the adventitia and media. Immunohistochemistry staining indicated increased expression of inducible nitric oxide synthase (iNOS), cleaved caspase-3, and S100A8/A9 (within in monocytes and neutrophils) proteins in coronary arteries of CI-1034-treated animals. However, there were similar expression levels of endothelial nitric oxide synthase (eNOS) among control and CI-1034-treated animals. Significant drug-related nitric oxide (NO) accumulation occurred on days 1 through 4 in serum. Increased interleukin (IL)-6 and fibrinogen in plasma and serum amyloid A (SAA) occurred on days 2 through 5 in CI-1034-treated animals. Increased levels of NO accumulation in serum; increased IL-6 and fibrinogen levels in plasma; increased SAA levels; and increased expressions of iNOS, cleaved caspase-3, and S100A8/A9 complex appear to be characteristic of CI-1034-induced acute vascular injury in dogs.

journal_name

Cardiovasc Toxicol

authors

McDuffie JE,Yu X,Sobocinski G,Song Y,Chupka J,Albassam M

doi

10.1385/ct:6:1:25

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

25-38

issue

1

eissn

1530-7905

issn

1559-0259

pii

CT:6:1:25

journal_volume

6

pub_type

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