Vascular hyperresponsiveness in perfused lungs from monocrotaline-treated rats.

Studies were conducted in isolated, buffer-perfused lungs to determine whether altered pulmonary vascular responsiveness could contribute to the evolution of monocrotaline (MCT)-induced pulmonary hypertension. Adult male rats were given a single subcutaneous injection of either 105 mg/kg MCT or its vehicle and vascular responsiveness to angiotensin II, ventilatory hypoxia (3% O2), and KCl was assessed in isolated, buffer-perfused lungs at 4, 7, and 14 days post-treatment. Relative to preparations derived from control animals, vasopressor responses induced by 0.

Pulmonary disposition and pharmacodynamics of verapamil.

Verapamil, a calcium channel blocker, has received recent attention as a potential therapeutic agent in pulmonary hypertension. Accordingly, the pulmonary disposition and pharmacodynamics of verapamil were evaluated in isolated rat lungs perfused at a constant rate with a physiological salt solution. Isolated rat lungs sequestered but did not metabolize verapamil.

Leu-enkephalin provokes naloxone-insensitive pulmonary vasoconstriction.

Leu-enkephalin evoked dose-dependent pulmonary vasoconstriction in isolated perfused rat lungs. The pressor responses were not attenuated by either naloxone or naltrexone nor were they mimicked by morphine. Blockade of histamine receptors with pyrilamine or blockade of serotonin receptors with methysergide also failed to antagonize leu-enkephalin-induced pulmonary vasoconstrictor responses.

Pulmonary vasoactivity of lung endocrine cell-related peptides.

Lung endocrine-like cells are believed to contain three immunohistochemically distinct peptides: bombesin, calcitonin, and Leu-enkephalin. Because these peptides exhibit smooth muscle stimulatory or inhibitory activity in some tissues, it has been suggested that their release from endocrine-like cells may influence airway or pulmonary vascular smooth muscle tone. To determine whether lung endocrine cell-related peptides could exert a regulatory influence in the pulmonary circulation, we evaluated their ability to constrict or dilate the vasculature of isolated perfused rat lungs.