Involvement of K^+ Channels and Na^+, K^+-ATPase in Relaxant Actions of Selective Phosphodiesterase 3 Inhibitors on Airway and Vascular Smooth Muscles Isolated from Guinea-pigs

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概要

• 論文の詳細を見る

• Milrinone or olprinone, a selective phosphodiesterase (PDE) 3 inhibitor, has relaxant actions on smooth muscles in addition to positive inotropic actions. The exact mechanism on vasodilating and bronchodilating actions of milrinone or olprinone has not been elucidated. In the present experiments, relaxant responses to PDE3 inhibitors were examined on the precontracted airway or pulmonary artery smooth muscle preparations to clarify their mechanism. Both milrinone and olprinone relaxed the airway smooth muscle preparation or the pulmonary artery preparation isolated from guinea-pigs in a concentration-dependent manner. In the airway smooth muscle, these relaxations were markedly blocked by iberiotoxin (a blocker of large conductance Ca^<2+>-activated K^+ channels). On the other hand, in the main pulmonary artery, the milrinone- and olprinone-induced relaxations were significantly blocked by iberiotoxin, and were more strongly blocked by ouabain (an inhibitor of Na^+, K^+-ATPase). In the right/left (R/L) pulmonary artery, ouabain also strongly blocked relaxant responses to milrinone and olprinone, but iberiotoxin did not modify these relaxations. Similar observations were seen on the bucladesine (a cyclic AMP mimic agent)-induced relaxation. In conclusion, milrinone and olprinone cause concentration-dependent relaxations of the isolated airway and pulmonary artery smooth muscles via an increase in intracellular cyclic AMP (cAMP). In the airway smooth muscle, large conductance Ca^<2+>-activated K^+ (BK_<Ca>) channels seem to play a crucial role for these relaxations. Relaxations of the main pulmonary artery induced by milrinone and olprinone are mediated predominantly by activation of Na^+, K^+-ATPase, and partly through BK_<Ca> channels. In the R/L pulmonary artery, vasorelaxant effects of milrinone and olprinone are more likely mediated by activation of Na^+, K^+-ATPase, but not BK_<Ca> channels.

• 獨協医科大学の論文

著者

• Uchida Kohsuke

  Department Of Pharmacology Dokkyo Medical University

• Tsurumi Tomoko

  Department of Intensive and Critical Care Medicine, Dokkyo Medical University

• Tsurumi Tomoko

  Department Of Intensive And Critical Care Medicine Dokkyo Medical University

• Uchida Kohsuke

  Department Of Pharmacology And Toxicology Dokkyo Medical University School Of Medicine

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