Protective role of nitric oxide donors on endothelium in ischemia-reperfusion injury: a meta-analysis of randomized controlled trials.

BACKGROUND: Decreased bioavailability of nitric oxide (NO) under hypoxic conditions can lead to endothelial dysfunction. NO supplementation may protect endothelial function in ischemia-reperfusion (IR) injury. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to verify the protective effect of NO donors on endothelium in IR injury. METHODS: Medline, Embase, Cochrane Library, and Web of Science databases were searched from inception to April 1, 2023. The specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing NO donors with placebo control groups; and (3) trials reporting the effects of these interventions on vascular endothelial functional outcomes in IR injury. Random-effects models were used to assess pooled effect sizes, which were expressed as standardized mean differences (SMD). RESULTS: Seven studies satisfied the inclusion criteria and consisted of a total of 149 participants. NO donors were protective of endothelial function in IR injury (SMD: - 1.60; 95% confidence interval [CI]: - 2.33, - 0.88, P < 0.0001; heterogeneity [I2 = 66%, P = 0.001]). Results of the subgroup analysis showed the following: absence of protective effect of NO donor use following ischemia on endothelial function in IR injury - 1.78 (95% CI: - 2.50, - 1.07) and loss of protective effect on endothelial function after prolonged NO donor use - 0.89 (95% CI: - 2.06, 0.28). CONCLUSION: The short-period use of NO donors before the onset of ischemia can protect endothelial function in IR injury.