Actions of SQ 29,548 on contractile responses and arachidonic acid metabolism of intrapulmonary arteries, in vitro.
This study was undertaken to investigate the influence of SQ 29,548, a thromboxane (TX) A2 receptor antagonist, on contractile responses and arachidonic acid (AA) metabolism of bovine intrapulmonary arterial (IPA) rings. The contractile responses to 5-hydroxytryptamine (5-HT), histamine, phenylephrine, and potassium chloride (KC1) were not significantly altered by 10(-8) M SQ 29,548 in either endothelium-intact or denuded IPA. The concentration of SQ 29,548 was chosen as it reduced the response to 10(-7) M U46619, a TXA2 mimetic, by 50%. AA metabolism by IPA produced more PGI2 whereas that by intrapulmonary vein (IPV) produced more PGE2. SQ 29,548 in concentrations of 10(-8) to 10(-5) M did not affect the activity of PGI2 synthase or GSH-dependent PGE2 isomerase in IPA or IPV microsomal fractions. No microsomal TXA2 synthase activity was detectable. SQ 29,548 had no effect on PGH synthase activity of IPA or IPV. The data indicate the presence of a TXA2-mediated contractile response in the IPA which is endothelium-independent and is selectively antagonized by SQ 29,548. The data further indicate that the contractile responses of IPA to 5-HT, histamine, phenylephrine, and KCl do not have a TXA2-mediated component. It is suggested that SQ 29,548 is a pharmacological probe to determine the role of TXA2 n pathophysiologic states in the pulmonary vascular bed and may be a therapeutic agent to treat pulmonary hypertensive disorders in which TXA2 is involved.
Boyd
V L
VL
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112.
Kvamme
P
P
Harbison
R
R
Kadowitz
P J
PJ
McNamara
D B
DB
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001158:Arteries / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002417:Cattle; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011463:Prostaglandins H / Q000378:metabolism; D011667:Pulmonary Veins / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D014661:Vasoconstriction / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D016718:Arachidonic Acid; D044262:Prostaglandin H2; D013928:Thromboxane A2; C045749:SQ 29548; D007213:Indomethacin