Local anaesthetics upregulate nitric oxide generation in cord blood and adult human neutrophils

Abstract

Nitric oxide (NO) generation by systemic neonatal neutrophils is not clarified. It is also not known whether local anaesthetics (LAs) transferred to the fetal systemic circulation following maternal epidural blockade may affect this process. In the present study, NO generation was evaluated in neutrophils from cord blood (CB, n = 11) and adult blood (n = 10) following exposure to bupivacaine (0.0005, 0.005, 1 mM), lidocaine (0.002, 0.02, 4 mM) and ropivacaine (0.0007, 0.007, 1.4 mM) using flow cytometry, as well as indirectly by determining nitrite concentrations in cell incubation media. To determine the role of NO synthase (NOS) isoforms in NO generation following exposure to LAs, experiments were repeated in the presence of the NOS inhibitors, NG-nitro-L-arginine methyl ester and aminoguanidine; in addition, the expression of NOS isoforms was analysed. CB neutrophils produced less NO than adult neutrophils. LAs, especially ropivacaine and lidocaine, stimulated neutrophil NO generation, but in CB neutrophils this effect was negligible at clinically relevant drug concentrations. A mechanism involving NOS activity was responsible for the observed phenomena. In conclusion, LAs are able to upregulate neutrophil NO production, but in neonates this effect is likely to be clinically insignificant.

In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro

“…is provides a common model [48][49][50][51][52]; that particular NOsystem involvement is also behind lidocaine-induced adverse effects. e inconsistent points about NO-system involvement, different L-NAME and/or different L-arginine effects, in various events, may be related to the facts that the NO-lidocaine studies rarely applied the used complete application of NO-agents (i.e., both L-NAME and L-arginine, given both alone and together) with the investigated procedure or agent application [53][54][55][56].…”

Giant phagocytes (Gφ) and neutrophil-macrophage hybrids in human carotid atherosclerotic plaques – An activated phenotype

“…However, the data are scarce for neutrophils. Yet, few studies show that all three NOS isoforms are present and generate NO in adult human neutrophils (35). Moreover, MPO, a major factor in oxidizing products in neutrophils was shown to produce nitrating oxidants in vivo (36).…”

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia

“…Recent studies have shown that lidocaine, in vitro and in humans (as well as in Kuli ńska's study of ropivacaine), enhanced NETosis in neutrophils at clinically relevant concentrations, thus having the possibility to change the course of inflammation and metastasis [118,119]. Kulinska et al also showed that LAs upregulate nitric oxide synthase (NOS) production by neutrophils, thus increasing NO synthesis [120]. Moreover, a recent meta-analysis showed that perioperative i.v.…”