title: Prostacyclin release and receptor activation: differential control of human pulmonary venous and arterial tone.
abstract: 1. In human pulmonary vascular preparations, precontracted arteries were more sensitive to the relaxant effect of acetylcholine (ACh) than veins (pD(2) values: 7.25+/-0.08 (n=23) and 5.92+/-0.09 (n=25), respectively). Therefore, the role of prostacyclin (PGI(2)) was explored to examine whether this mediator may be responsible for the difference in relaxation. 2. In the presence of the cyclooxygenase (COX) inhibitor, indomethacin (INDO), the ACh relaxations were reduced in arteries but not in veins. On the contrary, an inhibitor (l-NOARG) of the nitric oxide synthase blocked preferentially the relaxation in veins. 3. A greater release of 6-keto-PGF(1alpha), the stable metabolite of PGI(2), was observed in arterial preparations than in venous preparations when stimulated with either ACh or arachidonic acid (AA). 4. Exogenous PGI(2) produced a reduced relaxant effect in the precontracted vein when compared with the artery. In the presence of the EP(1)-receptor antagonist AH6809, the PGI(2) relaxation of veins was similar to arteries. 5. In veins, AA (0.1 mm) produced a biphasic response, namely, a contraction peak (0.4-0.5 g) followed by a relaxation. These contractions in venous preparations were abolished either in the absence of endothelium or in the presence of INDO or an EP(1)-receptor antagonist (AH6809, SC19220). In the arterial preparations AA induced only relaxations. 6. In both vascular preparations, COX-1 but not the COX-2 protein was detected in microsomal preparations derived from homogenized tissues or freshly isolated endothelial cells. 7. The differential vasorelaxations induced by ACh may be explained, in part, by a more pronounced production and release of PGI(2) in human pulmonary arteries than in the veins. In addition, while PGI(2) induced relaxation by activation of IP-receptors in both types of vessels, a PGI(2) constrictor effect was responsible for masking the relaxation in the veins by activation of the EP(1)-receptor.
authors.affiliation: CNRS UMR7131, Hopital Broussais, 102 rue Didot, 75014 Paris, France. xnorel@hotmail.com
authors.forename: Xavier
authors.initials: X
authors.lastname: Norel
authors.forename: Laurence
authors.initials: L
authors.lastname: Walch
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gascard
authors.forename: Vincent
authors.initials: V
authors.lastname: deMontpreville
authors.forename: Charles
authors.initials: C
authors.lastname: Brink
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000737:chemistry / Q000378:metabolism; D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000502:physiology*; D005260:Female; D005602:France; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011667:Pulmonary Veins / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D044004:Xanthones / Q000494:pharmacology
chemical_list: D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D044004:Xanthones; D012531:Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; D019335:Nitroarginine; D016718:Arachidonic Acid; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000109:Acetylcholine; D007213:Indomethacin