Enhancement of immunoreactivity for endothelin-1 and endothelin-converting enzyme-1 in the cadmium-treated rat thoracic aorta.
Male rats received daily intraperitoneal injections of cadmium sulfate (2.0 mg/kg) for 3, 6, and 8 days (cadmium-treated groups) or physiological saline for 8 days (control group). The thoracic aortae from both groups were used for electron microscopy and immunocytochemistry for big endothelin (ET)-1, ET-1 and ET-converting enzyme (ECE)-1, and the blood plasma and homogenized thoracic aortae were prepared for assays of big ET-1 and ET-1 concentrations. A remarkable increase in the number of Weibel-Palade (WP) bodies, enhanced immunoreactivities for ET-1 and ECE-1 along the endothelium, and elevated concentrations of ET-1 in the blood plasma as well as in homogenized thoracic aortae were observed in the cadmium-treated groups. However, immunoreactivity for big ET-1 and the plasma and aortic tissue concentrations of big ET-1 did not show any significant changes between the control and cadmium-treated groups. By immunoelectron microscopy, immunoreactivities for ET-1 and ECE-1 were much more pronounced in the increased WP bodies. Since WP bodies are involved in the extracellular release of ET-1 in the manner of a regulated pathway, these findings indicate that cadmium administration induces the enhanced release of ET-1, which is actively processed by ECE-1 in the WP bodies.
Department of Anatomy, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan. y-doi@med.uoeh-u.ac.jp
Yoshiaki
Y
Doi
Hideaki
H
Kudo
Osamu
O
Yamamoto
Kunshige
K
Hamasaki
Mitsuaki
M
Yoshizuka
Sunao
S
Fujimoto
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019187:Cadmium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007274:Injections, Intraperitoneal; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D020302:Weibel-Palade Bodies / Q000648:ultrastructure
D019187:Cadmium Compounds; D019332:Endothelin-1; D013431:Sulfates; C037123:cadmium sulfate; C492358:Ecel1 protein, rat; D008666:Metalloendopeptidases