title: Smooth muscle neurokinin-2 receptors mediate contraction in human saphenous veins.
abstract: Substance P (SP) and neurokinin A (NKA) are members of the tachykinin peptides family. SP causes endothelial-dependant relaxation but the contractile response to tachykinins in human vessels remains unknown. The objective was to assess the expression and the contractile effects of tachykinins and their receptors in human saphenous veins (SV). Tachykinin expression was assessed with RT-PCR, tachykinin receptors expression with RT-PCR and immunohistochemistry, and functional studies were performed in organ bath. Transcripts of all tachykinin and tachykinin receptor genes were found in SV. NK(1)-receptors were localized in both endothelial and smooth muscle layers of undistended SV, whereas they were only found in smooth muscle layers of varicose SV. The expression of NK(2)- and NK(3)-receptors was limited to the smooth muscle in both preparations. NKA induced concentration-dependent contractions in about half the varicose SV. Maximum effect reached 27.6±5.5% of 90 mM KCl and the pD(2) value was 7.3±0.2. NKA also induced the contraction of undistended veins from bypass and did not cause the relaxation of these vessels after precontraction. The NK(2)-receptor antagonist SR48968 abolished the contraction induced by NKA, and a rapid desensitization of the NK(2)-receptor was observed. In varicose SV, the agonists specific to NK(1)- or NK(3)-receptors did not cause either contraction or relaxation. The stimulation of smooth muscle NK(2)-receptors can induce the contraction of human SV. As SV is richly innervated, tachykinins may participate in the regulation of the tone in this portion of the low pressure vascular system.
authors.affiliation: Laboratory of Pulmonary Pharmacology, UPRES EA 220, Faculté de Médecine Île-de-France Ouest, University Versailles Saint Quentin, 11 rue Guillaume Lenoir, 92150 Suresnes, France.
authors.forename: Hakima
authors.initials: H
authors.lastname: Mechiche
authors.forename: Stanislas
authors.initials: S
authors.lastname: Grassin-Delyle
authors.forename: Francisco M
authors.initials: FM
authors.lastname: Pinto
authors.forename: Amparo
authors.initials: A
authors.lastname: Buenestado
authors.forename: Luz
authors.initials: L
authors.lastname: Candenas
authors.forename: Philippe
authors.initials: P
authors.lastname: Devillier
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D015260:Neprilysin / Q000235:genetics; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018039:Receptors, Tachykinin / Q000235:genetics; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology*; D015320:Tachykinins / Q000819:agonists / Q000235:genetics
chemical_list: D018041:Receptors, Neurokinin-2; D018039:Receptors, Tachykinin; D015320:Tachykinins; D015260:Neprilysin