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Endothelium‐dependent contraction in intrapulmonary arteries: mediation by endothelial NK 1 receptors and TXA 2
Author(s) -
Shirahase Hiroaki,
Kanda Mamoru,
Kurahashi Kazuyoshi,
Nakamura Shohei,
Usui Hachiro,
Shimizu Yoshiharu
Publication year - 1995
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.1476-5381.1995.tb15028.x
Subject(s) - neurokinin b , contraction (grammar) , nk1 receptor antagonist , antagonist , endothelium , thromboxane a2 , substance p , tachykinin receptor , medicine , chemistry , neurokinin a , endocrinology , receptor , receptor antagonist , pharmacology , biology , neuropeptide
1 We have examined whether three natural tachykinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) induce an endothelium‐dependent contraction (EDC) in the rabbit isolated intrapulmonary artery. 2 Removal of the endothelium almost abolished the contraction induced by SP (10 −8 m ) while it did not attenuate the contraction induced by SP (10 −7 m), NKA (10 −9 ‐10 −7 m) or NKB (10 −9 ‐10 −7 m). 3 The EDC induced by SP (10 −8 m) was abolished by NK 1 antagonists (FK‐888, CP‐96345, CP‐99994 and SR‐140333) but not by an NK 2 antagonist (SR‐48968). 4 The EDC induced by SP was attenuated by cyclo‐oxygenase inhibitors (aspirin and indomethacin), thromboxane A 2 (TXA 2 ) synthetase inhibitors (OKY‐046, KY‐234 and KY‐063) and a TXA 2 antagonist (S‐1452). 5 The rank order of potency causing endothelium‐independent contraction (EIC) was NKA>NKB>SP. The EIC induced by SP (10 −7 m) was attenuated by an NK 2 antagonist but not by NK 1 antagonists, cyclo‐oxygenase inhibitors, TXA 2 synthetase inhibitors or a TXA 2 antagonist. 6 In conclusion, SP at 10 −8 m induces EDC via endothelial NK 1 receptors and TXA 2 production, and SP at 10 −7 m induces EIC via NK 2 receptors in the rabbit intrapulmonary artery.