Characterization of thromboxane receptor blocking effects of SQ 29548 in the feline pulmonary vascular bed.
The effects of SQ 29548, a thromboxane (Tx) A2 receptor blocking agent, on responses to the TxA2 mimic U46619 were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 29548 in doses of 0.25-1 mg/kg iv reduced vasoconstrictor responses to U-46619; however, responses to prostaglandins (PG) F2 alpha and D2 and to serotonin were also decreased. After administration of SQ 29548 in doses of 0.05-0.1 mg/kg iv, responses to U-46619 and U-44069 were reduced significantly, and the dose-response curves for these TxA2 mimics were shifted to the right in a parallel manner at a time when responses to PGF2 alpha and PGD2 were not altered. The low doses of the TxA2 receptor blocking agent significantly reduced responses to the PG and TxA2 precursor arachidonic acid but were without significant effect on vasoconstrictor responses to serotonin; histamine; norepinephrine; angiotensin II; the major PGD2 metabolite 9 alpha,11 beta-PGF2; BAY K 8644, an agent that enhances calcium entry; and endothelin-1. The present data show that at low doses SQ 29548 selectively blocks TxA2 receptor-mediated responses in a competitive and reversible manner in the pulmonary vascular bed. These data suggest that responses to arachidonic acid are mediated in large part by the formation of TxA2 and provide evidence in support of the hypothesis that a discrete TxA2 receptor unrelated to PGF2 alpha or PGD2 receptors is present in undefined resistance vessel elements in the feline pulmonary vascular bed.
McMahon
T J
TJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Hood
J S
JS
Nossaman
B D
BD
Hyman
A L
AL
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors* / Q000502:physiology; D017482:Receptors, Thromboxane; D014661:Vasoconstriction / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548