Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening.

Abstract

Pulmonary hypertension (PH) is a progressive disease with a poor prognosis in which high pulmonary artery pressure leads to right heart failure, therefore, there is an urgent need to elucidate pathological mechanisms and to develop new treatment for PH. Minocycline has not only antibacterial effects but also anti-inflammatory effects in various tissues. We hypothesize that minocycline could prevent PH development in rats. PH was induced by a single intraperitoneal injection of monocrotaline (MCT, 60 mg/kg), and minocycline (20 mg/kg) was treated daily for 14 days from the day of MCT injection. Minocycline inhibited the rise in mean pulmonary arterial pressure of MCT-induced PH rats and improved the attenuation of acetylcholine-induced relaxation in isolated intrapulmonary artery from MCT-induced PH rats. Minocycline further inhibited vascular wall thickening of pulmonary arterioles and showed a tendency to inhibit the muscularization of pulmonary arterioles in MCT-induced PH rats. PH-preventing effect of minocycline does not seem to be mediated via the actions on matrix metalloproteinase, inflammatory cytokines, and mast cells migration in lung. In summary, we revealed for the first time that minocycline ameliorated the MCT-induced PH in rats, at least partly through preventing pulmonary artery endothelial dysfunction and wall thickening.