Pneumoperitoneum upregulates preproendothelin-1 messenger RNA.
BACKGROUND
Laparoscopic pneumoperitoneum has been shown to decrease glomerular filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a potent renal vasoconstrictor, has been implicated. The purpose of this study was to determine renal function, ET-1 gene expression, and peptide localization 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 insufflation. In the first group (n = 8), pneumoperitoneum (10 mmHg) was established for 30 min. The second group (n = 4) underwent a sham operation without pneumoperitoneum. In the final group (n = 4), kidneys were obtained from normal control animals without any prior surgical instrumentation. PreproET-1 (ppET-1) mRNA levels were measured by reverse transcription-polymerase 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 GFR 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 expression of ppET-1 mRNA in the laparoscopic group; it was 3.52 +/- 0.33 densitometric 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 expression of the ET-1 peptide in the vascular endothelium and proximal tubular cells of the laparoscopic group compared to the control and sham groups.


CONCLUSIONS
Pneumoperitoneum induces ET-1 gene and peptide upregulation in the kidney. Expression of ET-1 is increased in the renal vasculature and proximal tubular cells. The elevation of ET-1 and its localization may account for some of the renal dysfunction observed during pneumoperitoneum. This suggests that antagonism of ET-1 may be beneficial in patients with renal impairment undergoing prolonged laparoscopic procedures or in protecting allograft function during and after living donor nephrectomy.
Ambrose
J A
JA
Department of Surgery, Case Western Reserve University, University Hospitals of Cleveland, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
Onders
R P
RP
Stowe
N T
NT
Simonson
M S
MS
Robinson
A V
AV
Wilhelm
S
S
Schulak
J A
JA
D000818:Animals; D001483:Base Sequence; D019332:Endothelin-1 / Q000235:genetics*; D007677:Kidney Function Tests; D010535:Laparoscopy / Q000379:methods; D008297:Male; D023421:Models, Animal; D008969:Molecular Sequence Data; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects* / Q000379:methods; D011336:Probability; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D051437:Renal Insufficiency / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015854:Up-Regulation
D019332:Endothelin-1; D012333:RNA, Messenger