Capsaicin-sensitive nerves and neurokinins modulate non-neuronal nNOS expression in lung

We investigated the effects of substance P (SP) and neurokinin A (NKA) infusion and acute stimulation of capsaicin-sensitive sensory nerves fibers (CAP) on lung recruitment of neuronal nitric oxide synthase (nNOS)-positive inflammatory and respiratory sepithelial (RE) cells in guinea-pigs. We evaluated if the effects of CAP stimulation were maintained until 14 days and had functional pulmonary repercussions. After 24 h of CAP and 30 min after SP and NKA infusions there was an increase in nNOS-positive eosinophils and mononuclear cells compared to controls (P < 0.05). SP group presented an increase in nNOS-positive RE (P < 0.05). After 14 days of CAP stimulation, there was a reduction in resistance (Rrs) and elastance (Ers) of respiratory system in capsaicin pre-treated animals. We noticed a correlation between nNOS-positive eosinophils (R = −0.644, P < 0.05) and mononuclear cells (R = −0.88, P < 0.001) and Rrs. Concluding, CAP and neurokinins increase nNOS expression by inflammatory and RE cells. The increase in nNOS expression induced by low and high doses stimulation of CAP is longstanding and correlated to pulmonary mechanical repercussions.