Adverse effects of pneumoperitoneum on renal function: involvement of the endothelin and nitric oxide systems

Abstract

Increased intra-abdominal pressure (IAP) during laparoscopy adversely affects kidney function. The mechanism underlying this phenomenon is largely unknown. This study was designed to investigate the involvement of endothelin (ET)-1 and nitric oxide (NO) systems in IAP-induced renal dysfunction. Rats were subjected to IAP of 14 mmHg for 1 h, followed by a deflation for 60 min (recovery). Four additional groups were pretreated with 1) ABT-627, an ET_Aantagonist; 2) A-192621, an ET_Bantagonist; 3) nitroglycerine; and 4) N^G-nitro-l-arginine methyl ester, a NO synthase inhibitor, before IAP. Urine flow rate (V), absolute Na⁺excretion (U_NaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. Significant reductions in kidney function and hemodynamics were observed when IAP was applied. V decreased from 8.1 ± 1.0 to 5.8 ± 0.5 μl/min, U_NaV from 1.08 ± 0.31 to 0.43 ± 0.10 μeq/min, GFR from 1.84 ± 0.12 to 1.05 ± 0.06 ml/min (−46.9 ± 2.7% from baseline), and RPF from 8.62 ± 0.87 to 3.82 ± 0.16 ml/min (−54 ± 3.5% from baseline). When the animals were pretreated with either ABT-627 or A-192621, given alone or combined, the adverse effects of IAP on GFR, RPF, V, and U_NaV were significantly augmented. When the animals were pretreated with nitroglycerine, the adverse effects of pneumoperitoneum on GFR and RPF were substantially improved. In contrast, pretreatment with N^G-nitro-l-arginine methyl ester remarkably aggravated pneumoperitoneum-induced renal dysfunction. In conclusion, decreased renal excretory function and hypofiltration are induced by increased IAP. These effects are related to impairment of renal hemodynamics and could be partially ameliorated by pretreatment with nitroglycerine and aggravated by NO and ET blockade.