The effects of endothelins (ET) on the proliferative activity of the rat adrenal cortex have been investigated in vivo, using an in situ perfusion technique of the intact left gland. The chemicals were dissolved in the perfusion medium, and the perfusion continued for 120 min. ET-1 concentration dependently increased the mitotic index and [ 3 H]thymidine incorporation into DNA in the zona glomerulosa (ZG; 6-and 3-fold increases, respectively, at a 10 Ϫ8 M concentration), but not in the inner

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... enocortical layers, where the basal proliferative activity was negligible. The effect of 10 Ϫ8 M ET-1 was blocked by the ETA receptor antagonist BQ-123, whereas the ETB receptor antagonist BQ-788 was ineffective. ET-2 and ET-3 (10 Ϫ8 M) enhanced DNA synthesis in the ZG, but their effects were less intense than that of 10 Ϫ8 M ET-1 and were directly related to their binding potency for the ETA receptor subtype (ET-1 Ͼ ET-2 Ͼ Ͼ ET-3). The selective ETB receptor agonists BQ-3020, IRL-1620, and sarafotoxin-6B were inef-