TUBULAR HYPERTROPHY DUE TO WORK LOAD-INDUCED BY FUROSEMIDE IS ASSOCIATED WITH INCREASES OF IGF-1 AND IGFBP-1

We have examined the expression of insulin-like growth factor 1 (IGF-1 ), IGF binding protein-1 (IGFBP-1), and IGF binding protein-3 (IGFBP-3 ) in the rat distal nephron during increased cell work road and hypert rophy, induced by the diuretic, furosemide. Furosemide was given for s ix days to increase distal sodium delivery and uptake. To mitigate sal t loss, the animals drank 0.8% NaCl and 0.1% KCl. Control rats were in fused with vehicle (0.9% saline) and drank tap water. Furosemide incre ased urinary volume (13-fold) and sodium excretion (eightfold), and de creased urine osmolarity (fourfold). By immunocytochemistry, staining for IGF-1 and IGFBP-1 was markedly increased in distal convoluted tubu les and cortical collecting ducts; both segments also underwent hypert rophy. Increased staining for the peptides was evident early (1 hr, 18 hr) after furosemide, prior to hypertrophy of cells. Whereas transcri pts of IGF-1 and IGFBP-3 mRNA showed little or no increase in extracts from furosemide-treated kidney cortices, IGFBP-1 mRNA was increased t hreefold 18 hours after furosemide. Alterations of IGF-1 and IGFBP-1 w ere independent of changes in plasma aldosterone, glucocorticoids or a rginine vasopressin. That IGFBP-1 mRNA increased threefold without sig nificant changes in IGF-1 mRNA suggests that hypertrophic stimuli migh t initially induce the synthesis of IGF binding protein followed by th e trapping of extracellular IGF-1. The present study raises the possib ility of IGF-1 and IGFBP-1 being involved in processes that lead to tu bular hypertrophy. IGFBP-1 may regulate these effects by binding to an d interaction with IGF-1.