Stretch-induced contraction of rabbit isolated pulmonary artery and the involvement of endothelium-derived thromboxane A2.
1. The mechanism of stretch-induced contraction of the intrapulmonary artery of rabbit was studied with special regard to the endothelium-dependence and production of prostanoids. 2. Isolated intrapulmonary artery of rabbits in ring form produced contraction when stretched slowly up to 180% of its initial muscle length (= 100%) at a rate of 0.44 mm s-1, with a stimulus period of 5 min. 3. The stretch-induced contraction was attenuated by the mechanical removal of the endothelium, inhibitors of cyclo-oxygenase such as aspirin and indomethacin, [1S-[1 alpha,2 alpha (Z),3 alpha,4 alpha]]-7-[3-[[2-[(phenylamino)carbonyl] hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-y1]-5-heptenoic acid (SQ 29,548), which is a thromboxane A2/prostaglandin H2 receptor antagonist, or by ozagrel, an inhibitor of thromboxane A2 synthase. 4. Biochemical assay indicated that the production of thromboxane B2, a stable metabolite of thromboxane A2, was increased 17 times in response to stretch only when the endothelium was intact. The production of thromboxane B2 was also inhibited by aspirin or ozagrel. 5. The production of 6-keto prostaglandin F1 alpha, a stable metabolite of prostacyclin, was also increased in response to stretch in the preparation with intact endothelium. However, ozagrel showed no apparent effect on the production of 6-keto prostaglandin F1 alpha. 6. These results suggest that a mechanical stimulus like stretch can act on endothelial cells of rabbit pulmonary artery to cause contraction by activation of arachidonic acid metabolism via the cyclooxygenase pathway and subsequent release of thromboxane A2 and/or an increase in the ratio of thromboxane A2/prostacyclin.
Nakayama
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, University of Shizuoka, Japan.
Ueta
K
K
Tanaka
Y
Y
Tanabe
Y
Y
Ishii
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D011311:Pressoreceptors / Q000502:physiology*; D011651:Pulmonary Artery / Q000502:physiology*; D011817:Rabbits; D013928:Thromboxane A2 / Q000502:physiology*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D014661:Vasoconstriction
D004791:Enzyme Inhibitors; D008689:Methacrylates; D013928:Thromboxane A2; D011464:Epoprostenol; D013930:Thromboxane-A Synthase; C034364:ozagrel; D000109:Acetylcholine; D002118:Calcium