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Effects of adrenomedullin and calcitonin gene‐related peptide on airway and pulmonary vascular smooth muscle in guinea‐pigs
Author(s) -
Pinto Arthur,
Sekizawa Kiyohisa,
Yamaya Mutsuo,
Ohrui Takashi,
Jia Yu Xia,
Sasaki Hidetada
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16061.x
Subject(s) - adrenomedullin , calcitonin gene related peptide , guinea pig , calcitonin , medicine , vascular smooth muscle , endocrinology , biology , smooth muscle , neuropeptide , receptor
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 gene‐related peptide (CGRP). 2 In tracheal rings, CGRP (1 nM to 1 μ m ) potentiated the cholinergic contractions induced by electrical field stimulation (EFS) at 5 Hz in a concentration‐dependent manner. At a concentration of 1 μ m , 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 μ m ) did not alter either EFS‐induced cholinergic or ACh‐induced contractions. 3 In bronchial strips, CGRP (1 nM to 1 μ m ) slightly reduced both the non‐adrenergic non‐cholinergic (NANC) contraction induced by EFS at 10 Hz and the substance P (1 μ m )‐induced contraction in a concentration‐dependent manner, whereas adrenomedullin (1 nM to 1 μ m ) was without effect. 4 Neither CGRP (1 μ m ) nor adrenomedullin (1 IXM) altered NANC relaxation induced by EFS at 5 Hz in tracheal rings precontracted with histamine (10 μ m ). 5 Adrenomedullin (1 nM to 1 μ m ) and CGRP (1 nM to 1 μ m ) induced a concentration‐dependent relaxation of the histamine (10 μ m )‐ and prostaglandin F 2α (10 μ m )‐precontracted pulmonary arterial rings with intact endothelium with a similar potency. 6 Neither removal of the endothelium nor N G ‐nitro‐L‐arginine methyl ester (100 μ m ) altered the vasorelaxant effects of adrenomedullin (1 nM to 1 μ m ) and CGRP (1 nM to 1 μ m ). 7 The putative CGRP receptor antagonist, CGRP 8–37 (1 μ m to 10 μ m ) 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 CGRP 1 receptors.