ARGININE-VASOPRESSIN GENE-EXPRESSION IN RATS WITH PUROMYCIN-INDUCED NEPHROTIC SYNDROME

Nephrotic syndrome is characterized by water and sodium retention, whi ch leads to edema formation. The nonosmotic stimulation of arginine va sopressin (AVP) release from the pituitary gland has been implicated t o be one of the important factors of abnormal water retention in patie nts with nephrotic syndrome. It is not known, however, whether nephrot ic syndrome is associated with stimulation of hypothalamic vasopressin gene expression. Puromycin aminonucleoside is known to cause altered glomerular permeability, which results in experimental nephrotic syndr ome in rats. In the present study, therefore, AVP gene expression has been studied in the hypothalamus of rats with puromycin aminonucleosid e-induced nephrotic syndrome (PNS). Nephrotic syndrome was induced by a single intravenous injection of puromycin aminonucleoside (50 mg/kg body weight). Nephrotic syndrome was confirmed by urinary protein excr etion (control 20.8 +/- 3.5 mg/24 hr v PNS 273.9 +/- 41.4 mg/24 hr; P < 0.0001, n = 6) and serum albumin concentrations (control 4.52 +/- 0. 07 g/dL v PNS 2.96 +/- 0.22 g/dL; P < 0.001, n = 6). In PNS rats, plas ma AVP was significantly higher than in control rats (control 0.77 +/- 0.10 pg/mL v PNS 2.13 +/- 0.42 pg/mL; P < 0.005, n = 12), even though there were no differences in plasma osmolality (control 292.0 +/- 2.0 mOsm/kg H2O v PNS 290.3 +/- 2.5 mOsm/kg H2O; P = NS, n = 12) or serum sodium concentration (control 142.7 +/- 0.7 v PNS 142.1 +/- 1.1; P NS , n = 12). Hypothalamic AVP mRNA determined by solution hybridization was significantly increased in PNS rats (control 2,915 +/- 545 pg/hypo thalamus v PNS 5,914 +/- 1,161 pg/hypothalamus; P < 0.05, n = 12). The se results, therefore, provide support for the increased hypothalamic AVP biosynthesis and increased release of AVP from the pituitary gland in rats with PNS. (C) 1995 by the National Kidney Foundation, Inc.