TRPV1 Agonist Capsaicin Attenuates Lung Ischemia-Reperfusion Injury in Rabbits

Abstract

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) agonist, was found to protect against myocardial and renal ischemia-reperfusion (IR) injury. This study was carried out to investigate the role of capsaicin in lung IR injury in vivo. Forty male New Zealand rabbits were randomized into four groups (10 per group) as follows: sham group (sham thoracotomy), IR group (occlusion of the left pulmonary hilus for 1 h followed by reperfusion for 3 h), CAP (capsaicin) group (a bolus injection of CAP 5 min before ischemia), CPZ (capsazepine) group (a bolus injection of the TRPV1 antagonist CPZ 5 min before ischemia). Blood and lung tissue samples were obtained for blood gas and biochemical analyses, wet/dry weight ratio measurements, and histologic evaluation. Protein levels and neutrophils in the bronchoalveolar lavage fluid (BALF) were also measured. Pretreatment with capsaicin improved gas exchange function, decreased lung wet/dry ratio and protein levels and neutrophil counts in BALF, decreased lung malondialdehyde levels and myeloperoxidase activities, increased superoxide dismutase activities, along with an elevation of calcitonin gene-related peptide (CGRP) level (P < 0.05 versus IR group). Capsaicin also attenuated IR-induced pathological lesions. By contrast, capsazepine exacerbated gas exchange abnormality, increased pulmonary microvascular permeability, oxidative stress, neutrophils infiltration, and also revealed a decreased CGRP level (P < 0.05 versus IR group). Results from the present study show that capsaicin confers protection against lung IR injury. These protective effects seem to be closely related to the inhibition of inflammation and oxidative stress via the activation of TRPV1 and the release of CGRP.