1 The airway and pulmonary vascular effects of adrenomedullin were studied in the guinea-pig isolated trachea, main bronchi and pulmonary artery in vitro and compared to the effects of calcitonin generelated peptide (CGRP).2 In tracheal rings, CGRP (1 nM to 1 gM) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration-dependent manner. At a concentration of 1 gM, CGRP slightly decreased the responses to log EFS frequency, producing 50% of the maximum contraction from a control value of 0.77+0.10 Hz to 0.54+0.05 Hz without a significant effect on the concentration-response curves to acetylcholine (ACh). In contrast, adrenomedullin (1 nM to 1 gM) did not alter either EFS-induced cholinergic or ACh-induced contractions. 3 In bronchial strips, CGRP (1 nm to 1 pM) slightly reduced both the non-adrenergic non-cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 gM)-induced contraction in a concentration-dependent manner, whereas adrenomedullin (1 nM to 1 pM) was without effect.4 Neither CGRP (1 gM) nor adrenomedullin (1 gM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 gM). Adrenomedullin (1 nm to 1 gM) and CGRP (1 nM to 1 pM) induced a concentration-dependent relaxation of the histamine (10 pM)-and prostaglandin F2a (10 gM)-precontracted pulmonary arterial rings with intact endothelium with a similar potency.6 Neither removal of the endothelium nor NG-nitro-L-arginine methyl ester (100 pM) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 pM) and CGRP (1 nM to 1 gM). 7 The putative CGRP receptor antagonist, CGRP8-37 (1 MM to 10 gM) concentration-dependently attenuated the CGRP (3 nM to 30 nM)-induced vasorelaxant actions, whereas it had no effect on the relaxation of vessel rings induced by adrenomedullin (3 nM to 30 nM). 8 These results suggest that adrenomedullin is a potent vasodilator of the pulmonary artery without any bronchomotor effect in the guinea-pig lung, and that the vasorelaxant actions of adrenomedullin are not mediated via the activation of CGRP1 receptors.
To determine whether psychological factors affect the cough response, we employed a classical conditioning procedure in which capsaicin challenge was paired with the presentation of an odor in awake guinea pigs. On days 1-4, animals received combined administrations of the unconditioning stimulus, capsaicin aerosols, and the contidioning stimulus, camphor aerosols (group 1), capasaicin and saline aerosols (group 2), and camphor and saline aerosols (group 3), and the number of coughs was counted. On day 5, all groups received camphor and saline aerosols. A significant number of coughs (p<0.01) was observed only in group 1 when the animals were exposed to the odor alone on day 5. This suggests that associative learning enhances the cough response.
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