THROMBOXANE MEDIATES GLOMERULAR HEMODYNAMICS IN A MODEL OF CHRONIC GLOMERULAR-DISEASE

In order to evaluate a possible haemodynamic role of cyclooxygenase products in chronic renal disease, a model of chronic glomerular injury was induced in nephritic rats by unilateral nephrectomy and high dietary protein intake. Eight weeks after induction of an in situ immune complex glomerulonephritis (ICGN), rats subjected to high protein (HP) intake (42% protein) and uninephrectomy revealed a significantly lower glomerular filtration rate (GFR; 485 +/- 53-mu-l min-1 100 g-1 body weight (BW)) compared with uninephrectomized rats with ICGN which were on low protein (LP) diet (6% protein) (825 +/- 155-mu-l min-1 100 g-1 BW) (P < 0.01). The glomerular thromboxane B2 (TxB2) formation in uninephrectomized rats with ICGN on either LP or HP intake was not significantly different (HP: 473 +/- 61; LP: 493 +/- 63 pg mg-1 min-1), but was significantly higher when compared with non-nephritic controls on either diet. Glomerular prostaglandin E2 (PGE2) production in rats on HP diet was higher compared with rats with LP intake (HP: 617 +/- 67; LP: 351 +/- 76 pg mg-1 min-1) (P < 0.01). The thromboxane receptor blocker daltroban significantly elevated suppressed GFR in ICGN rats on HP diet (ICGN + vehicle: 426 +/- 69; ICGN + daltro: 689 +/- 66-mu-l min-1 100 g-1 BW) (P < 0.01). Thromboxane receptor blockade had no effect on glomerular haemodynamics in ICGN animals receiving LP diet (ICGN + vehicle: 771 +/- 24; ICGN + daltro: 684 +/- 85-mu-l min-1 100 g-1 BW). The cyclooxygenase inhibitor indomethacin reduced the already compromised GFR in ICGN animals on HP diet (ICGN + vehicle: 533 +/- 54; ICGN + indo: 335 +/- 43-mu-l min-1 100 g-1 BW) (P < 0.05), but was without effect on GFR in nephritic rats on LP intake (ICGN + vehicle: 785 +/- 102; ICGN + indo: 633 +/- 89-mu-l min-1 100 g-1 BW). These data demonstrate that eicosanoids modulate glomerular haemodynamics in a model of chronic glomerular disease induced by immune complex formation, uninephrectomy and HP intake.