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Mechanism underlying substance P‐induced relaxation in dog isolated superficial temporal arteries
Author(s) -
Enokibori Mikiko,
Okamura Tomio,
Toda Noboru
Publication year - 1994
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.1476-5381.1994.tb14026.x
Subject(s) - endothelium , chemistry , endocrinology , medicine , tetraethylammonium , nitric oxide , ouabain , glibenclamide , vasodilation , prostacyclin , substance p , biochemistry , potassium , sodium , neuropeptide , receptor , organic chemistry , diabetes mellitus
1 In helical strips of dog superficial temporal arteries with intact endothelium, substance P elicited a concentration‐related relaxation with an EC 50 of 2.8 (2.4–3.2) × 10 −10 M. 2 The relaxant response to the peptide in low concentrations (1–4 × 10 −10 M) sufficient to produce approximately half maximal relaxation was not inhibited by indomethacin, but was markedly suppressed by N G ‐nitro‐ l ‐arginine ( l ‐NOARG), a nitric oxide (NO) synthase inhibitor, and by endothelium denudation. 3 High concentration (10 −7 M) of substance P produced marked relaxations in endothelium‐intact strips. Removal of the endothelium attenuated the relaxation, and indomethacin or tranylcypromine suppressed the endothelium‐independent relaxation. In indomethacin‐treated strips with intact endothelium, l ‐NOARG attenuated but did not abolish the relaxation. The residual, l ‐NOARG‐resistant relaxation was not significantly inhibited by ouabain, glibenclamide or tetraethylammonium. 4 Substance P (10 −7 M) increased the levels of cyclic GMP and cyclic AMP. The increase in cyclic GMP was abolished by endothelium denudation and treatment with l ‐NOARG, whereas the cyclic AMP increment was abolished by indomethacin. 5 Three different mechanisms may be involved in the substance P‐induced relaxation: (1) an endothelium‐dependent relaxation mediated by the release of NO from the endothelium, resulting in an increase of cyclic GMP (low and high concentrations of the peptide); (2) an endothelium‐independent relaxation in association with cyclic AMP increment caused by prostaglandin I 2 released from sub‐endothelial tissues (high concentration), and (3) another endothelium‐dependent relaxation possibly mediated by unidentified mediator(s) released from the endothelium (high concentration).