α7 Nicotinic acetylcholine receptor contributes to the alleviation of lung ischemia-reperfusion injury by transient receptor potential vanilloid type 1 stimulation.J Surg Res. 2018 10; 230:164-174.JS
Activation of transient receptor potential vanilloid type 1 (TRPV1) decreases lung ischemia-reperfusion injury (LIRI) in rabbits and rats. Stimulation of α7 nicotinic acetylcholine receptors (α7nAChRs) protects against lung injury. Here we examined whether α7nAChRs contribute to TRPV1-mediated protection against LIRI.
Wild-type (WT) and TRPV1-knockout (KO) mice were subjected to 1-h lung ischemia by clamping left hilum, followed by 2-h reperfusion. WT or KO mice were pretreated with vehicle, TRPV1 agonist capsaicin, TRPV1 antagonist capsazepine, α7nAChR antagonist methyllycaconitine, or α7nAChR agonist PNU-282987. Arterial blood and lung tissues were obtained for blood gas, lung wet-to-dry weight ratio, interleukin (IL)1β, IL6, tumor necrosis factor-α (TNF-α), apoptosis-related proteins (caspases, Bax, Fas), and pathologic scoring.
Capsaicin pretreatment reduced wet-to-dry ratio, pathologic score, alveolar-arterial oxygen gradient (A-aDO2), and IL1β, IL6, and TNFα levels in WT mice, with no effects in KO mice. This reduction was reversed by TRPV1 blockade. Furthermore, α7nAChR blockade before capsaicin exacerbated LIRI as evidenced by enhanced alveolar-arterial oxygen gradient, pathologic score, and IL1β, IL6, and TNFα levels, while α7nAChR agonist pretreatment under TRPV1 blockade showed opposite changes. Capsaicin also decreased cleaved caspase-3, caspase-3/9, and Bax protein expression, effects abolished by TRPV1 blockade. Similarly, α7nAChR blockade diminished capsaicin-induced downregulation of apoptotic proteins, and α7nAChR activation decreased expression levels even under TRPV1 blockade.
TRPV1 activation alleviates LIRI, partially dependent on α7nAChR activity. The α7nAChR stimulation with or without existence of TRPV1 alleviates LIRI. Thus, α7nAChR is involved in the pathway of TRPV1-mediated protection against LIRI and the specific mechanism remains to be revealed.