Histopathological and immunohistochemical studies on arteritis induced by fenoldopam, a vasodilator, in rats.
Fenoldopam, a dopaminergic (DA1) agonist, has been reported to induce medial necrosis and adventitial inflammatory response in the splanchnic arteries in rats. This study was carried out to clarify the detailed time course of the inflammatory responses, using antibodies for the inflammatory cell markers, CD3 (T cell), CD20 (B cell) and ED-1 (macrophage), and inflammatory serum factors, IgG, IgM and C3. Rats were administered fenoldopam for 24 hours by intravenous infusion. Histopathologically, medial necrosis with hemorrhage was observed at the end of infusion, but it almost disappeared on day 7 post-infusion. Adventitial inflammatory responses with ED-1-, CD3- and CD20-positive cells were very slight at the end of infusion, became prominent with marked fibrosis on days 3 and 5, decreased on day 7, and subsided on day 14. The serum factors were first present in the area of medial necrosis, then shifted to the subendothelial space or cytoplasm of smooth muscle cells, and disappeared on day 14 post-infusion. Gaps in the external elastic lamina were observed on days 3 and 5 post-infusion, and IgG and IgM were present outside the gaps in the adventitia. These results provided us with more detailed information on the inflammatory responses following medial damage induced by vasodilators.
Ikegami
H
H
Yamanouchi Pharmaceutical Co., Ltd., and Department of Veterinary Pathology, Faculty of Agriculture, The University of Tokyo, Japan. ikegami@yamanouchi.co.jp
Shishido
T
T
Ishida
K
K
Hanada
T
T
Nakayama
H
H
Doi
K
K
D000818:Animals; D018951:Antigens, CD20 / Q000032:analysis; D001167:Arteritis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D004815:Epidermal Growth Factor / Q000032:analysis; D018818:Fenoldopam / Q000633:toxicity*; D019084:Fluorescent Antibody Technique, Indirect; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D066257:Heparin-binding EGF-like Growth Factor; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007262:Infusions, Intravenous; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014665:Vasodilator Agents / Q000633:toxicity*
D018951:Antigens, CD20; D015415:Biomarkers; D017252:CD3 Complex; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D036341:Intercellular Signaling Peptides and Proteins; D014665:Vasodilator Agents; D004815:Epidermal Growth Factor; D018818:Fenoldopam