Inhibition of urea tubular reabsorption by PGE1 infusion in man

We have shown that the inhibition of prostaglandin (PG) synthesis in man decreases the fractional clearance of urea (FC(urea). To understand the mechanism(s) by which PG affect the renal handling of urea, 6 normal volunteers were randomly studied in maximal antidiuresis (by water deprivation and by administering 1-desamino-8-D-arginine vasopressin) before and during PGE₁ infusion, in two separate occasions: (A) after 7 days of normal protein (1 g/kg b.w./day) and water intake (10 ml/kg b.w./day), and (B) after 7 days of low protein intake (0.5 g/kg b.w./day) and high water intake (80 ml/kg b.w./day) to lower the corticomedullary osmotic gradient. During infusion of PGE₁ at rates of 0.01, 0.05 and 0.1 μg/min/kg, randomly administered, the urinary fluid losses were replaced by infusing equal volumes of hypotonic NaCl (80 mmol/l). To evaluate the time effects of this protocol, control studies were performed in an other 8 subjects receiving vehicle infusion without PGE₁. In study A, FC(urea) rose by 23% (p <0.01) at the lowest PGE₁ infusion rate (0.01 μg/min/kg), in the absence of any simultaneous change in water and salt output, Uosm, PAH and inulin clearance. Higher PGE, infusion rates (0.05 and 0.1 μg/min/kg) were associated with a progressive increase of FC(urea) (50 %, p1 caused the same changes of FC(urea) and the other parameters as in study A. FC(urea) was directly related to dose infusion of PGE₁ both in study A and B (p1 infusion, is: (1) not associated with change in tubular handling of salt and water at the lowest infusion of PGE₁; (2) not mediated by passive hydrosmotic forces or by antagonism with ADH; (3) dependent on the dose of exogenous PGE₁.