The impact of intra-abdominal hypertension on gene expression in the kidney

Intra-abdominal hypertension (IAH) has been recognized as a source of morbidity and mortality in the injured patient. Research concerning this entity has focused predominantly on the pathophysiology. We developed a model of IAH to determine whether gene expression is altered in the presence of this condition.

Using general anesthesia, adult Sprague-Dawley rats were intubated and instrumented with a carotid and jugular catheter. Three pairs of rats (three control; three IAH 25 mm Hg) were used at each time interval. Continuous measurements of heart rate, blood pressure, cardiac output, and temperature were recorded. Arterial blood gases were measured every 30 minutes. A catheter was placed in the peritoneum and warm saline was infused up to a pressure of 25 mm Hg that was measured through this catheter continuously. At 30 and 60 minutes, the kidneys were harvested and standard protocols were used to extract nucleic acid and perform cDNA microarray analysis screening for 4,000 genes. Each experimental rat was paired with a control rat and each set underwent individual cDNA array analysis.

Hemodynamic changes occurred that were consistent with IAH, including depression of cardiac output and acidosis. Although widespread changes in gene expression were identified, only genes that were up-regulated and down-regulated by a ratio of fivefold, a difference in magnitude of 150 molecular dynamic counts, and p < 0.05 were considered significant. When comparing IAH of 25 mm Hg at 30 and 60 minutes, there was a surprising decrease in up-regulated genes from 10 to 1. In addition, there was an increase in down-regulated genes from zero to five genes.

IAH causes changes in gene up- and down-regulation in the kidney. The number and types of genes change in magnitude and type over time. Further investigation into renal gene expression may offer insight into the molecular pathophysiology of IAH.