Effect of intermedin/adrenomedullin 2 on the pulmonary vascular bed in hypoxia-induced pulmonary hypertensive rats

This study aimed to investigate the effect and mechanism of action of intermedin/adrenomedullin (IMD/AM ) on the pulmonary vascular bed in pulmonary hypertensive rats. Male Sprague-Dawley rats were exposed to hypobaric hypoxia for 3 weeks to induce pulmonary hypertension (PHT). The development of PHT was confirmed by histopathological analyses and measurement of hematocrit, basal perfusion pressure, and right ventricle hypertrophy. Subsequently, the effect of IMD/AM in pulmonary hypertensive rats was assessed with both, isolated organ bath and isolated lung perfusion studies. In the PHT group, the basal perfusion pressure and % hematocrit were increased, and right ventricle hypertrophy occurred after 3 weeks of hypoxia exposure. Increased medial wall thickness was also observed in the pulmonary artery with histopathological analysis. In the PHT, the nitric oxide-mediated vasodilation caused by IMD/AM in the pulmonary vascular bed and this was as potent as the control group. Acetylcholine responses were also protected in pulmonary hypertensive rats. Our results showed for the first time in in vitro studies that IMD/AM administration causes potent, concentration-dependent vasodilation in the main and resistance pulmonary arteries of rats with PHT. Based on these results, IMD/AM might be considered as a future therapeutic target for PHT treatment.