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

Abstract

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.

Sodium Nitrite Attenuates Reduced Activity of Vascular Matrix Metalloproteinase-2 and Vascular Hyper-Reactivity and Increased Systolic Blood Pressure Induced by the Placental Ischemia Model of Preeclampsia in Anesthetized Rats

“…Indeed, nitrite has been considered a bioactive storage reservoir for NO, and reducing nitrite to NO has been considered a pharmacological strategy to restore circulating NO levels [ 13 ]. Interestingly, the nitrite reduction to NO seems to occur mainly in conditions of hypoxia, acidosis, and ischemia [ 14 , 15 , 16 , 17 , 18 ]. As demonstrated in a previous study in vitro, inorganic nitrite vasodilated human placental arteries obtained after cesarean sections following uncomplicated pregnancies [ 15 ].…”

Investigation of NO Role in Neural Tissue in Brain and Spinal Cord Injury

“…There are numerous studies on the use of NO donors as neuroprotective agents after ischemic injury [40][41][42][43][44][45]. It has been found that short-term use of NO donors before the beginning of ischemia can protect the function of endothelium in ischemic reperfusion injury [46]. It was also shown that inhalation of NO or nitrite encourages brain function during perinatal hypoxic and chemical intervention [47].…”