RESPONSE AND SENSITIVITY OF ISOLATED HUMAN PULMONARY MUSCLE PREPARATIONS TO PHARMACOLOGICAL AGENTS

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Abstract
The responsiveness (g/mm2) and sensitivity (pD2 value) of various agonists were examined in isolated stored human bronchial and pulmonary arterial and venous preparations. In isolated bronchial muscles, large preparations (internal diameter about 6 mm) were less responsive (g/mm2) to contractile agents than smaller preparations (internal diameter .apprx. 2 mm). Noncumulative concentration-effect curves were produced in bronchial preparations using histamine, acetylcholine, carbachol and Ba. Histamine contracted both bronchial and vascular preparations whereas 5-hydroxytryptamine contracted only vascular tissues. The latter effect was always blocked by either methylsergide or ketanserin. 5-Hydroxytryptamine relaxed bronchial tissues that were contracted with either histamine, acetylcholine or prostaglandin E2. This relaxation was not antagonized by methysergide, ketanserin, propranolol or indomethacin. Dimaprit and 4-methyl histamine were without effect in isolated contracted bronchial preparations. Vasoactive intestinal peptide, Substance P and platelet-activating factor when added to preparations at resting tone failed to induce a contraction. These agents did not relax histamine-contracted isolated human pulmonary muscle preparations. Anti-immunoglobulin E antibody sometimes contracted isolated human bronchial muscle but not pulmonary vascular preparations. These data were difficult to assess because of the variations observed. Anti-immunoglobulin G antibody was inactive. Noradrenaline [norepinephrine] did not elicit a physiological response in isolated bronchial muscle preparations at concentrations which always induced a contraction in the pulmonary vascular preparations. In the presence of propranolol, noradrenaline neither contracted nor relaxed isolated human bronchial preparations. The sensitivity of isolated bronchial muscle preparations to isoproterenol, salbutamol and theophylline were determined. Although there was a large range of sensitivity to isoproterenol in histamine-contracted isolated human bronchial preparations (pD2 value between 9.40 and 6.52), all bronchial preparations from the same lung sample were similar in sensitivity. A functional antagonism exists between carbachol and isoproterenol in isolated human bronchial muscle preparations as the sensitivity to isoproterenol was reduced in those preparations contracted with this agonist. There is a large variation in responsiveness to contractile agonists in isolated human pulmonary muscle preparations, the histamine sensitivity of bronchial and pulmonary vascular muscle preparations is approximately the same, there is no physiological relaxant response to H2 receptor stimulation in isolated human bronchial muscle preparations and the lack of an effect of noradrenaline in the absence and presence of .beta. blockade suggests that this agonist may not be important in the regulation of human airway muscle responses. Whereas the 5-hydroxytryptamine contractile effect in isolated vascular preparations is antagonized by methysergide and ketanserin, the relaxant response in bronchial preparations cannot be prevented by these classical serotonin antagonists.

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