Minocycline inhibits endothelin-1-induced contraction in isolated pulmonary artery

Pulmonary hypertension (PH) still requires both elucidation of pathological mechanisms and development of new treatment agents. We previously reported that an intraperitoneal administration of minocycline prevented monocrotaline-induced PH in rats. However, the direct vasodilatory effects of minocycline on isolated pulmonary artery are unclear. We then investigated them in rat isolated intrapulmonary arteries (IPAs). In both endothelium-intact and -denuded IPAs, minocycline (10 μg/ml) inhibited endothelin-1 (40 nM)- or high-K⁺ (72.7 mM)-induced precontraction. In endothelium-intact IPAs, indomethacin (10 μM) significantly inhibited the relaxation. We revealed for the first time that minocycline indues vasodilation through both endothelium-dependent and -independent mechanisms in isolated IPAs.