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.