# Glucagon-like peptide-1 stimulates acute secretion of pro-atrial natriuretic peptide from the isolated, perfused pig lung exposed to warm ischemia

## TL;DR

This study shows that liraglutide, a GLP-1 receptor agonist, increases the release of pro-atrial natriuretic peptide in pig lungs during ex vivo perfusion.

## Contribution

The novel finding is that GLP-1 receptor activation stimulates local secretion of proANP in the lung, independent of heart-derived sources.

## Key findings

- Liraglutide significantly increased proANP secretion in isolated perfused pig lungs.
- The effect was observed within the first 30 minutes of perfusion.
- No differences in oxygenation or inflammatory markers were found between groups.

## Abstract

Glucagon-like peptide-1 (GLP-1) has proven to be protective in animal models of lung disease but the underlying mechanisms are unclear. Atrial natriuretic peptide (ANP) is mainly produced in the heart. As ANP possesses potent vaso- and bronchodilatory effects in pulmonary disease, we hypothesised that the protective functions of GLP-1 could involve potentiation of local ANP secretion from the lung. We examined whether the GLP-1 receptor agonist liraglutide was able to improve oxygenation in lungs exposed to 2 h of warm ischemia and if liraglutide stimulated ANP secretion from the lungs in the porcine ex vivo lung perfusion (EVLP) model. Pigs were given a bolus of 40 µg/kg liraglutide or saline 1 h prior to sacrifice. The lungs were then left in vivo for 2 h, removed en bloc and placed in the EVLP machinery. Lungs from the liraglutide treated group were further exposed to liraglutide in the perfusion buffer (1.125 mg). Main endpoints were oxygenation capacity, and plasma and perfusate concentrations of proANP and inflammatory markers. Lung oxygenation capacity, plasma concentrations of proANP or concentrations of inflammatory markers were not different between groups. ProANP secretion from the isolated perfused lungs were markedly higher in the liraglutide treated group (area under curve for the first 30 min in the liraglutide group: 635 ± 237 vs. 38 ± 38 pmol/L x min in the saline group) (p < 0.05). From these results, we concluded that liraglutide potentiated local ANP secretion from the lungs.