Effect of Neurohypophysial Hormones on Protein Excretion by the Kidneys

Vasopressin (VP) is one of the main factors affecting intraglomerular hemodynamics, filtration pressure, and the state of mesangial cells contributing to proteinuria progression. The aim of this work was to study the effect of neurohypophysial hormones (VP and oxytocin, OT) on urinary protein excretion. Experiments were carried out on Wistar rats, healthy and with microalbuminuria caused by minimal damage to the glomerular filter. Microalbuminuria was modeled by the administration of D-nitroarginine methyl ester (D-NAME, 50 mg/kg, intraperitoneally). VP (0.05 and 1.5 nmol/kg) and OT (0.15 nmol/kg) were administered to rats intramuscularly, V 2 -antagonist (15 nmol/kg) and V 1a -antagonist (20 nmol/kg) intraperitoneally. To reduce the level of endogenous VP, animals were loaded with water (10 mL/kg) via orogastric gavage; urine was then collected for 2 h, and the levels of total protein, albumin, β 2 -microglobulin, and immunoglobulin G (IgG) were analyzed. In healthy rats, VP at a dose of 0.05 nmol/kg and OT did not affect albumin excretion, but VP at a dose of 1.5 nmol/kg provoked microalbuminuria. In a model of glomerular filter impairment induced by D-NAME administration, VP at a dose of 0.05 nmol/kg and OT led to the normalization of albumin excretion, while VP at a dose of 1.5 nmol/kg caused pronounced proteinuria: albumin excretion increased by 100 times, IgG by 10 times. Blockade of V 2 receptors aggravated protein loss induced by D-NAME and VP (1.5 nmol/kg), while blockade of V 1a receptors prevented it. Thus, at high concentrations in the blood, VP enhances protein filtration in the kidney. This effect is mediated via V 1a receptors and, depending on the barrier properties of the glomerular filter, leads to the development of microalbuminuria or severe proteinuria. OT and VP (at a dose at which it predominantly activates V 2 receptors) have an antiproteinuric effect. The revealed effects of neurohypophysial hormones on albumin excretion open up new promising therapeutic targets for the correction of glomerular dysfunctions.