Although it has been suggested that overproduction of nitric oxide (NO) is responsible for death during endotoxic shock or sepsis, recent studies indicate that NO inhibition under such conditions is detrimental. The reason for these seemingly controversial findings may be because most studies were not standardized, ie, they were conducted at different stages of sepsis.
To determine whether differential alterations in endothelium-derived NO occur at different stages of sepsis.
Design, Intervention, and Main Outcome Measures:
Rats were subjected to sepsis by cecal ligation and puncture (CLP) or sham operation, followed by injection of 3 mL/100 g of body weight saline solution. At 2, 3.5,10, or 20 hours after CLP, the thoracic aorta was isolated and responses to an endothelium-dependent vasodilator, acetylcholine (via NO), and an endothelium-independent vasodilator, nitroglycerine (directly providing NO) were determined.
Endothelium-dependent relaxation increased at 2 hours (ie, very early after the onset of sepsis), returned to sham levels at 3.5 hours, but decreased at 10 and 20 hours after CLP (ie, later stage of hyperdynamic sepsis and hypodynamic sepsis, respectively). Moreover, the acetylcholine concentration, required to produce half-maximum relaxation, decreased at 2 hours but increased at 20 hours after CLP. No significant difference in nitroglycerine-induced relaxation was seen, however, in the tested groups. The increased vascular relaxation at 2 hours after CLP was not due to the upregulation of prostacyclin since cyclooxygenase inhibition did not reverse this phenomenon.
This study points out the complexity of the alterations in NO production with the progression of sepsis. The triphasic response of endothelium-derived NO should be taken into account when attempting to manipulate NO levels during sepsis.(Arch Surg. 1994;129:1137-1143)
Wang P, Ba ZF, Chaudry IH. Nitric Oxide: To Block or Enhance Its Production During Sepsis? Arch Surg. 1994;129(11):1137–1143. doi:10.1001/archsurg.1994.01420350035003
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