Sustained Elevated Levels of Circulating Vasopressin Selectively Stimulate the Proliferation of Kidney Tubular Cells via the Activation of V2 Receptors

The hypothalamic hormone vasopressin (AVP) has known mitogenic effects on various cell types. This study was designed to determine whether sustained elevated levels of circulating AVP could influence cell proliferation within adult tissues known to express different AVP receptors, including the pituitary, adrenal gland, liver, and kidney. Plasmatic AVP was chronically increased by submitting animals to prolonged hyperosmotic stimulation or implanting them with a AVP-containing osmotic minipump. After several days of either treatment, increased cell proliferation was detected only within the kidney. This kidney cell proliferation was not affected by the administration of selective V-1a or V-1b receptor antagonists but was either inhibited or mimicked by the administration of a selective V-2 receptor antagonist or agonist, respectively. Kidney proliferative cells mostly concerned a subpopulation of differentiated tubular cells known to express the V-2 receptors and were associated with the phosphorylation of ERK. These data indicate that in the adult rat, sustained elevated levels of circulating AVP stimulates the proliferation of a subpopulation of kidney tubular cells expressing the V-2 receptor, providing the first illustration of a mitogenic effect of AVP via the activation of the V-2 receptor subtype. (Endocrinology 150: 239-250, 2009)