Neurokinins Induce Relaxation of Human Pulmonary Vessels Through Stimulation of Endothelial NK1 Receptors

The effects of neurokinins and neurokinin receptor selective agonists have been investigated on human intralobar pulmonary vessels. Substance P (SP) and [SarMet(O2)]SP, a selective NK1 receptor agonist, induced concentration-dependent relaxation of pulmonary vessels precontracted with phenylephrine....

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Bibliographic Details
Published in:	Journal of cardiovascular pharmacology Vol. 41; no. 3; pp. 343 - 355
Main Authors:	Mechiche, Hakima, Koroglu, Alexandre, Candenas, Luz, Pinto, Francisco M, Birembaut, Philippe, Bardou, Marc, Elaerts, Jacques, Devillier, Philippe
Format:	Journal Article
Language:	English
Published:	Philadelphia, PA Lippincott Williams & Wilkins, Inc 01-03-2003 Hagerstown, MD Lippincott
Subjects:	Aged Biological and medical sciences Blood vessels and receptors Dose-Response Relationship, Drug Endothelium, Vascular - drug effects Endothelium, Vascular - physiology Female Fundamental and applied biological sciences. Psychology Humans In Vitro Techniques Male Middle Aged Pulmonary Artery - drug effects Pulmonary Artery - physiology Pulmonary Veins - drug effects Pulmonary Veins - physiology Receptors, Neurokinin-1 - agonists Receptors, Neurokinin-1 - physiology Substance P - pharmacology Tachykinins - pharmacology Vasodilation - drug effects Vasodilation - physiology Vertebrates: cardiovascular system Human Tachyphylaxis Substance P Lung Peptide hormone Acetylcholine-Human-Neurokinin-Pulmonary artery-Pulmonary vein Neuropeptide In vitro Pulmonary artery Neurokinin B Neurokinin A Blood vessel Acetylcholine Pulmonary vein Biological receptor
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Summary:	The effects of neurokinins and neurokinin receptor selective agonists have been investigated on human intralobar pulmonary vessels. Substance P (SP) and [SarMet(O2)]SP, a selective NK1 receptor agonist, induced concentration-dependent relaxation of pulmonary vessels precontracted with phenylephrine. The mean negative log (M) EC50 values for SP and [SarMet(O2)]SP were 8.6 and 8.9, respectively, on arterial preparations and 8.9 and 8.6, respectively, on venous preparations. Relaxations to [SarMet(O2)]SP were abolished by the NK1 receptor antagonist SR140333. The relaxations to a second application of [SarMet(O2)]SP were markedly reduced, suggesting a rapid desensitization of the NK1 receptor. Such desensitization was not observed with acetylcholine. The selective NK2 receptor agonist, [Nle]NKA, and the selective NK3 receptor agonist, [MePhe]NKB, caused neither contractions nor relaxations of pulmonary vessels. The NK1 receptor-mediated relaxations were abolished by removing the endothelium or by a combination of N-nitro-L-arginine and indomethacin, whereas each compound exerted a partial inhibitory effect. Similar results were observed with acetylcholine. Positive immunostaining for NK1 receptors was only found in the endothelium. Reverse transcription-polymerase chain reaction detected messenger RNA for NK1 receptors without any detection of messenger RNA for NK2 or NK3 receptors. In conclusion, human pulmonary arteries and veins express endothelial NK1 receptors that mediate relaxation through a combination of cyclooxygenase and nitric oxide activities and are subjected to rapid tachyphylaxis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0160-2446 1533-4023
DOI:	10.1097/00005344-200303000-00002