IMPAIRED RENAL-FUNCTION IN OBSTRUCTIVE-JAUNDICE - ENHANCED GLOMERULARTHROMBOXANE SYNTHESIS AND EFFECTS OF THROMBOXANE RECEPTOR BLOCKADE INBILE DUCT-LIGATED RATS

1. Patients with obstructive jaundice are especially susceptible to ac ute renal failure. We have previously observed that in rats with bile duct ligation impaired renal function is associated with increased uri nary thromboxane excretion. 2. In the present study we therefore inves tigated, in rats with bile duct ligation, renal function, urinary thro mboxane excretion and thromboxane B-2 synthesis by isolated glomeruli as well as the effects of the thromboxane A(2)/prostaglandin H-2 recep tor antagonist Daltroban on renal function in rats with bile duct liga tion as compared with sham-operated rats. 3. On the fourth day after b ile duct ligation (n=7 rats) endogenous creatinine clearance as an est imate of glomerular filtration rate was significantly reduced to 0.74/-0.05 (SEM) as compared with 1.06+/- 0.09 ml min(-1) g(-1) kidney wei ght in sham-operated rats (n=7, P<0.01). In rats with bile duct ligati on, urine volume was slightly increased, whereas urinary sodium (Na+) (P<0.001) and potassium (K+) (P<0.01) excretion as well as urine osmol arity (P<0.05) were significantly reduced and lower than in sham-opera ted rats. 4. Urinary thromboxane excretion was significantly higher in rats with bile duct ligation than in sham-operated rats: 116.6+/-22.3 versus 56.8+/-10.2 pmol 24 h(-1) 100 g(-1) body weight (P<0.05). Thro mboxane B-2 synthesis in glomeruli isolated from rats with bile duct l igation was also significantly higher than in sham-operated rats: 12.6 +/-2.0 versus 6.4+/-0.9 pmol h(-1) mg(-1) protein (P<0.05). 5. The thr omboxane A(2)/prostaglandin H-2 receptor antagonist Daltroban normaliz ed glomerular filtration rate in a second group of rats with bile duct ligation (n=7) to 1.03+/-0.08 (P<0.01) and slightly increased it in s ham-operated rats (n=7) to 1.24+/- 0.11 ml min(-1) g(-1) kidney weight (not significant). Daltroban, while without effects on urine volume a nd osmolarity in sham-operated rats, further increased urine volume an d decreased osmolarity in rats with bile duct ligation after surgery. After surgery Daltroban reduced fractional Na+ and K+ excretion in sha m-operated rats and in rats with bile duct ligation. 6. The results su ggest that obstructive jaundice following bile duct ligation is associ ated with enhanced renal glomerular thromboxane A(2) synthesis, which suppresses glomerular filtration rate and predisposes to acute renal f ailure. Treatment with Daltroban, a specific thromboxane A(2)/prostagl andin H-2 receptor antagonist, restores glomerular filtration rate to normal, probably secondary to normalization of disturbed intrarenal bl ood flow following bile duct ligation.