Endothelin receptor antagonists prevent parathyroid cell proliferation caused by hypocalcemia in rats.

Abstract

Secondary hyperparathyroidism in chronic renal failure is one of the most frequently encountered disorders of calcium homeostasis, characterized by parathyroid hypertrophy and hyperplasia. It is important to understand the pathogenesis of parathyroid epithelial cell hyperplasia and to determine the factors involved in the parathyroid cell proliferation for the development of the new therapeutic strategy for the secondary hyperparathyroidism. The existence of the endothelin system in the parathyroid gland and the involvement of the endothelin system in the proliferation of parathyroid cells have recently been demonstrated. The purpose of this review is to summarize the recent findings on the role of the endothelin system in the parathyroid cell proliferation, and to discuss the effect of the endothelin receptor antagonists for the treatment of the secondary hyperparathyroidism. It was recently demonstrated that the inhibitory effect of endothelin receptor antagonist, bosentan, on the proliferation of parathyroid cells in secondary hyperparathyroidism rats induced by the low calcium diet. The treatment of the low calcium diet rats with bosentan was found to substantially reduce the number of PCNA-positive parathyroid cells, wet weight of parathyroid gland, and serum PTH level. The effectiveness of the endothelin receptor antagonists for the prevention of the low calcium diet-induced secondary hyperparathyroidism in rats has been clearly demonstrated. These findings suggest the possibility that endothelin receptor antagonist might become one of the important therapeutic strategies for preventing secondary hyperparathyroidism in humans.