Pneumoperitoneum upregulates preproendothelin-1 messenger RNA

Background: Laparoscopic pneumoperitoneum has been shown to decrease glomer ular filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a po tent renal vasoconstrictor, has been implicated. The purpose of this study was to determine renal function, ET-1 gene expression, and peptide localiza tion in kidneys subjected to CO2 pneumoperitoneum. Methods: Experiments were performed in three groups of anesthetized Sprague -Dawley rats in which GFR and UV were measured before, during, and after in sufflation. In the first group (n = 8), pneumoperitoneum (10 mmHg) was esta blished for 30 min. The second group (n = 4) underwent a sham operation wit hout pneumoperitoneum. In the final group (n = 4), kidneys were obtained fr om normal control animals without any prior surgical instrumentation. Prepr oET-1 (ppET-1) mRNA levels were measured by reverse transcription-polymeras e chain reaction (RT-PCR). The ET-1 peptide was localized within kidneys by immunohistochemistry (IHC). Results: Pneumoperitoneum caused a significant (p < 0.05) 87% decrease in G FR and a 79% decrease in UV from baseline, with a return to baseline values after desufflation. RT-PCR showed a significant (p < 0.05) increase in exp ression of ppET-1 mRNA in the laparoscopic group; it was 3.52 +/- 0.33 dens itometric units (DU), as compared to 0.35 +/- 0.06 DU and 0.57 +/- 0.12 DU in the control and sham groups, respectively. IHC showed enhanced expressio n of the ET-1 peptide in the vascular endothelium and proximal tubular cell s of the laparoscopic group compared to the control and sham groups. Conclusion: Pneumoperitoneum induces ET-1 gene and peptide upregulation in the kidney. Expression of ET-1 is increased in the renal vasculature and pr oximal tubular cells. The elevation of ET-1 and its localization may accoun t for some of the renal dysfunction observed during pneumoperitoneum. This suggests that antagonism of ET-1 may be beneficial in patients with renal i mpairment undergoing prolonged laparoscopic procedures or in protecting all ograft function during and after living donor nephrectomy.