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.
|Number of pages||7|
|Publication status||Published - 1992|
- Antidiuretic hormone
- Corticomedullary osmotic gradient
- Tubular reabsorption of urea
ASJC Scopus subject areas