Increased cerebral and renal endothelial nitric oxide synthase gene expression after cardiopulmonary bypass in the rat

Objective

Hemodilution and endothelial nitric oxide synthase genetic polymorphism may contribute to cerebral and renal injury after cardiopulmonary bypass. This study tested the hypothesis that cardiopulmonary bypass and anemia stimulate an increase in cerebral and renal endothelial nitric oxide synthase gene expression in an experimental model of cardiopulmonary bypass.

Methods

Anesthetized rats underwent a sham procedure without cardiopulmonary bypass (sham, n = 5), normothermic bypass for 1 hour (CPB, n = 7), or bypass plus hemodilutional anemia (CPB anemia, n = 9). After 24 hours of recovery, RNA was extracted from the cerebral cortex, renal cortex, and renal medulla. Quantitative reverse transcriptase polymerase chain reaction was used to assess endothelial nitric oxide synthase messenger RNA levels in brain and kidney tissues.

Results

The hemoglobin concentration of anemic CPB rats was significantly lower than that of nonanemic rats on bypass (64 ± 5 vs 99 ± 8 g · L⁻¹, P < .001). Cerebral cortical endothelial nitric oxide synthase messenger RNA levels were increased after cardiopulmonary bypass relative to those of the sham group (11.2 ± 4.2 vs 6.3 ± 1.5 fg, P = .031), without a further increase in anemic rats. Renal medullary endothelial nitric oxide synthase messenger RNA levels were significantly higher in the CPB anemia group than in the sham and CPB groups (7.1 ± 4.4 fg vs 1.8 ± 0.4 fg vs 3.0 ± 0.6 fg, P < .001). Renal cortical endothelial nitric oxide synthase messenger RNA levels did not change significantly.

Conclusions

Normothermic cardiopulmonary bypass was associated with higher endothelial nitric oxide synthase messenger RNA levels in kidney and brain than was the sham procedure 24 hours after cardiopulmonary bypass. Anemia accentuated the increase in renal medullary, but not cerebral cortical, endothelial nitric oxide synthase expression. These data provide an approach for exploring potential mechanisms by which endothelial nitric oxide synthase may contribute to renal and cerebral dysfunction after cardiopulmonary bypass and anemia.

CTSNet classification: 1, 7, 19, 25, 29

Abbreviations and Acronyms: cDNA, complementary DNA, CPB, cardiopulmonary bypass, eNOS, endothelial nitric oxide synthase, IP, intraperitoneal, IV, intravenous, nNOS, neuronal nitric oxide synthase, NOS, nitric oxide synthase, PCR, polymerase chain reaction, RT-PCR, reverse transcriptase polymerase chain reaction, VEGF, vascular endothelial growth factor