title: 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(A) antagonist; 2) A-192621, an ET(B) antagonist; 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(Na)V), 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 microl/min, U(Na)V from 1.08 +/- 0.31 to 0.43 +/- 0.10 microeq/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(Na)V 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.
authors.affiliation: Department of Physiology & Biophysics, Ruth & Bruce Rappaport Faculty of Medicine, Technion, Isarel Institute of Technology, Haifa, 31096, Israel. abassi@tx.technion.ac.il
authors.forename: Zaid
authors.initials: Z
authors.lastname: Abassi
authors.forename: Bishara
authors.initials: B
authors.lastname: Bishara
authors.forename: Tony
authors.initials: T
authors.lastname: Karram
authors.forename: Samer
authors.initials: S
authors.lastname: Khatib
authors.forename: Joseph
authors.initials: J
authors.lastname: Winaver
authors.forename: Aaron
authors.initials: A
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000077868:Atrasentan; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000502:physiology; D044023:Receptor, Endothelin B / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology; D017595:Renal Plasma Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: C120508:A 192621; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin; D019331:NG-Nitroarginine Methyl Ester; D000077868:Atrasentan