Regulatory role of prostanoids in glomerular microcirculation of remnant nephrons

The glomerular microcirculation of the remnant nephron is characterized by reduced afferent (R(A)) and efferent (R(E)) arteriolar resistances and markedly increased single nephron glomerular plasma flow and filtration rates. We investigated the role of prostanoid production in mediating these adaptive alterations in glomerular hemodynamics after the reduction of renal mass. Acute administration of indomethacin, 5 mg/kg iv in anesthetized euvolemic, Sprague-Dawley rats with intact kidneys led to no significant alteration in renal hemodynamics, whereas in similarly prepared subtotally nephrectomized rats such inhibition significantly reduced remnant kidney glomerular filtration rate from 0.57 ± 0.07 to 0.45 ± 0.05 ml/min and single nephron glomerular filtration rate (SNGFR) from 93 ± 4 to 72 ± 5 nl/min. This reduction of SNGFR was due to diminutions in the glomerular ultrafiltration coefficient (K(f)) from basal values of 0.061 ± 0.004 to 0.050 ± 0.004 nl·s^-1·mmHg^-1 and in initial glomerular capillary plasma flow rate (Q̇(A)) from 416 ± 42 to 321 ± 42 nl/min. The decrease in Q̇(A) was a consequence of proportional increases in R(A) and R(E). In other groups of animals we demonstrated that urinary excretions of both vasodilatory as well as vasoconstrictor prostanoids per surviving nephron increase several fold in subtotally nephrectomized rats compared with rats with intact kidneys and that administration of indomethacin, 5 mg/kg iv, reduced urinary excretions of both vasodilatory prostaglandins, prostaglandin E and 6-keto-prostaglandin F(1α), as well as vasoconstrictor prostanoid, thromboxane B₂, to the same degrees in both subtotally nephrectomized rats and rats with intact kidneys. We conclude that after the reduction of renal mass adaptive increments in synthesis of both vasodilatory and vasoconstrictor prostanoids occur in surviving nephrons. The hemodynamic effects of prostaglandins on R(A) and R(E) and on K(f) account, at least in part, for the increments in single nephron glomerular plasma flow and filtration rates.