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1 Physiology and Biophysics, Faculty of Medicine, Technion, Haifa, Israel
2 General Surgery A, Rambam Medical Center, Haifa, Israel
3 Vascular Surgery & Transplantation, Rambam Medical Center, Haifa, Israel
4 Department of Anesthesiology, Rambam Medical Center, Haifa, Israel
5 Department of Physiology and Biophysics, The Bruce Rappaport Faculty of Medicine, Haifa, Israel
6 Vascular Surgery and Kidney Transplantation, Rambam Medical Center, Haifa, Israel
* To whom correspondence should be addressed. E-mail: abassi{at}tx.technion.ac.il.
Background: Increased intra-abdominal pressure (IAP) during laparoscopy adversely affects kidney function. The mechanism underlying this phenomenon is largely unknown. Objective: This study was designed to investigate the involvement of Endothelin-1 (ET-1) and nitric oxide (NO) systems in IPA-induced renal dysfunction. Methods: Rats were subjected to IAP of 14 mmHg for 1h followed by a deflation for 60 min (recovery). Four additional groups were pretreated with: 1) ABT-627, an ETA antagonist, 2) A-192621, an ETB antagonist, 3) nitroglycerine-NTG, 4) L-NAME, NOS inhibitor before IAP. Urine flow rate (V), absolute and fractional Na+ excretion (UNaV, FENa, respectively) and glomerular filtration rate (GFR), renal plasma flow (RPF), were determined. Results: Significant reductions in kidney function and hemodynamics were observed when IAP was applied: V decreased from 8.1±1.0 to 5.8±0.5µl/min, UNaV from 1.08±0.31 to 0.43±0.1 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 UNaV were significantly augmented. When the animals were pretreated with NTG, the adverse effects of pneumoperitoneum on GFR and RPF were substantially improved. In contrast, pretreatment with L-NAME remarkably aggravated pneumoperitoneum-induced renal dysfunction. 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 NTG, and aggravated by NO and ET blockade.
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