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 [Sar(9) Met(O(2)) ]SP(11), a selective NK(1) receptor agonist, induced concentration-dependent relaxation of pulmonary vessels precontracted with phenylephrine. The mean negative log (M) EC (50) values for SP and [Sar (9) Met(O2))]SP(11) were 8.6 and 8.9, respectively, on arterial preparations and 8.9 and 8.6, respectively, on venous preparations. Relaxations to [Sar(9) Met(O(2) ) ]SP were abolished by the NK receptor antagonist SR140333. The relaxations to a second application of [Sar(9) Met(O (2)) ]SP were markedly reduced, suggesting a rapid desensitization of the NK(1) receptor. Such desensitization was not observed with acetylcholine. The selective NK receptor agonist, [Nle(10)]NKA, and the selective NK (3) receptor agonist, [MePhe(7)]NKB, caused neither contractions nor relaxations of pulmonary vessels. The NK(1) receptor-mediated relaxations were abolished by removing the endothelium or by a combination of -nitro-L-arginine and indomethacin, whereas each compound exerted a partial inhibitory effect. Similar results were observed with acetylcholine. Positive immunostaining for NK(1) receptors was only found in the endothelium. Reverse transcription-polymerase chain reaction detected messenger RNA for NK(1) receptors without any detection of messenger RNA for NK(2) or NK(3) receptors. In conclusion, human pulmonary arteries and veins express endothelial NK(1) receptors that mediate relaxation through a combination of cyclooxygenase and nitric oxide activities and are subjected to rapid tachyphylaxis.
Mechiche
Hakima
H
Laboratory of Vascular Pharmacology, Faculty of Medicine, Reims, France.
Koroglu
Alexandre
A
Candenas
Luz
L
Pinto
Francisco M
FM
Birembaut
Philippe
P
Bardou
Marc
M
Elaerts
Jacques
J
Devillier
Philippe
P
D000368:Aged; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D011667:Pulmonary Veins / Q000187:drug effects* / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000819:agonists* / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D018040:Receptors, Neurokinin-1; D015320:Tachykinins; D013373:Substance P