Contribution of vasopressin to progression of chronic renal failure: Studyin Brattleboro rats

We have previously shown that a chronic reduction in plasma vasopressin lev el slowed the progression of chronic renal failure (CRF) in Sprague Dawley rats. The aim of the present study was to determine the respective contribu tion of presser (V1) and antidiuretic (V2) effects of vasopressin on progre ssion. Male homozygous Brattleboro rats with hereditary central diabetes in sipidus were submitted to 5/6 nephrectomy. They were divided into three gro ups, two of which received chronic i.p. infusion of AVP (V1 + V2 effects) o r dDAVP (V2 effects). The third group served as control (CONT). The doses o f AVP and dDAVP were chosen so as to produce urine osmolality similar to th at observed in 5/6 Nx Sprague Dawley rats. All rats ate the same amount of food and drank water ad libitum. Renal function was studied for 13 weeks. A ll three groups showed a marked hypertension. Rats infused with dDAVP, but not those infused with AVP, had a higher creatininemia, anemia and urinary protein excretion than CONT rats. In the dDAVP but not the AVP group, fract ional excretion of urea was markedly decreased and plasma urea concentratio n rose much more than that of creatinine. These results show that V2 but no t V1 effects play a major role in the deleterious influence of vasopressin on progression, at least in Brattleboro rats. The more severe progression s een in dDAVP rats could indirectly result from the V2-mediated effects on t he collecting duct resulting in a decreased efficiency of urea excretion, a n increased intrarenal urea recycling, and a rise in plasma urea concentrat ion. Both the toxic effects of urea and the recently demonstrated V2-mediat ed increase in glomerular hemodynamics might be involved in the deleterious influence of V2 agonism.