RAT RENAL FUNCTION FOUR DAYS AFTER BILE-DUCT LIGATION: EFFECTS OF INDOMETHACIN AND VASOACTIVE AGENTS

Abstract

The purpose of this study was to assess the effects of the cyclooxygenase inhibitor, indomethacin, and some vasoactive agents on the renal functional parameters during the early liver injury induced by four days bile duct ligation (BDL). Wistar rats with four days-BDL and control-sham operated were used. Renal function was measured in anesthetized rat treated with a single dose of indomethacin (control, 0.3, 1.0, 3.0 mg/kg b.w.; i.v.) one hour before clearance studies. Sulindac effects were also evaluated (5 mg/kg b.w., i.p). Isolated rat kidney preparations from control and BDL donor rats were used to study renal vascular response to noradrenaline, carbachol or sodium nitroprusside. The bile duct ligation promoted a diminished renal cortical plasma flow (RCPF) on the fourth day post surgery accompanied with a diminution in the glomerular filtration rate (GFR), increased filtration fraction and increased fractional excretion of water and sodium. Indomethacin 0.3 mg/kg induced an increase in GFR and RCPF, maintaining the high filtration fraction in BDL rats. The other doses did not alter these parameters as compared with bile duct ligated rats without treatment, but indomethacin 3 mg/kg caused a significant increase in filtration fraction. Indomethacin induced dose-dependent diminution in natriuresis in sham and BDL groups. Sulindac did not modify hemodynamic parameters, but induced antinatriuresis and antidiuresis in both experimental groups. Maximal vascular responses to noradrenaline measured in isolated rat kidneys were statistically diminished in BDL-rats as compared with controls (C, n = 7; 35.0 ± 2.3 mmHg ml⁻¹ min; BDL-rats, n = 5; 23.8 ± 0.7 mmHg ml⁻¹ min; p<0.02), without changes in EC₁₅. Maximal relaxation induced by sodium nitroprusside in the phenylephrine (PHE)-pre-constricted renal vasculature in control preparations did not differ from that observed in BDL group (C: n = 6; 49.5 ± 2.3%). Values of EC₅₀ were 1.26 ± 0.07 µM (n = 6) in control preparations and 0.34 ± 0.03 µM (n = 4) in kidneys from BDL-rats (p<0.001). Carbachol induced a biphasic relaxation of PHE-pre-constricted renal vasculature. No differences in maximal responses were found. EC₅₀ value of the second phase in BDL group was significantly decreased compared to control preparations (C: n = 6, 0.47 ± 0.05 µM; BDL: n = 6, 0.22 ± 0.03 µM; p<0.001). The present results show that the altered renal function after a short time post bile duct ligation is determined, at least in part, by increased release of arachidonic derivatives in vascular bed and tubular cells. At this stage of liver injury, the alteration in the renal vascular response to different vasoactive agents is remarkable.

• Bile duct ligation
• Renal function
• Renal vascular response
• Isolated rat kidney