Impaired renal function in obstructive jaundice: enhanced glomerular thromboxane synthesis and effects of thromboxane receptor blockade in bile duct-ligated rats.
1. Patients with obstructive jaundice are especially susceptible to acute renal failure. We have previously observed that in rats with bile duct ligation impaired renal function is associated with increased urinary thromboxane excretion. 2. In the present study we therefore investigated, in rats with bile duct ligation, renal function, urinary thromboxane excretion and thromboxane B2 synthesis by isolated glomeruli as well as the effects of the thromboxane A2/prostaglandin H2 receptor antagonist Daltroban on renal function in rats with bile duct ligation as compared with sham-operated rats. 3. On the fourth day after bile duct ligation (n = 7 rats) endogenous creatinine clearance as an estimate 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 weight in sham-operated rats (n = 7, P < 0.01). In rats with bile duct ligation, urine volume was slightly increased, whereas urinary sodium (Na+) (P < 0.001) and potassium (K+) (P < 0.01) excretion as well as urine osmolarity (P < 0.05) were significantly reduced and lower than in sham-operated 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). Thromboxane B2 synthesis in glomeruli isolated from rats with bile duct ligation 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).(ABSTRACT TRUNCATED AT 250 WORDS)
Kramer
H J
HJ
Department of Medicine, University of Bonn, Federal Republic of Germany.
Schwarting
K
K
Bäcker
A
A
D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002779:Cholestasis / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000378:metabolism; D008026:Ligation; D009929:Organ Size; D010648:Phenylacetates / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis
D010648:Phenylacetates; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013929:Thromboxane B2; D013928:Thromboxane A2; C051762:daltroban