Influence of SQ 30741 on thromboxane receptor-mediated responses in the feline pulmonary vascular bed.
The effects of SQ 30741, a thromboxane A2 (TxA2) receptor blocking agent, on responses to the TxA2 mimic, U-46619, were investigated in the pulmonary vascular bed of the intact-chest cat under constant-flow conditions. The administration of SQ 30741 in doses of 1-2 mg/kg iv markedly reduced vasoconstrictor responses to U-46619 without altering responses to prostaglandin (PG) F2 alpha or PGD2 and serotonin. SQ 30741 had no significant effect on mean vascular pressures in the cat, and the dose-response curve for U-46619 was shifted to the right in a parallel manner with a similar apparent maximal response. In addition to not altering responses to PGF2 alpha, PGD2 alpha, or serotonin, SQ 30741 (2 mg/kg iv) was without significant effect on pulmonary vasoconstrictor responses to the PGD2 metabolite 9 alpha, 11 beta-PGF2, norepinephrine, angiotensin II, BAY K 8644, endothelin 1, or endothelin 2. Although responses to vasoconstrictor agents, which act through a variety of mechanisms, were not altered, responses to the PG and TxA2 precursor, arachidonic acid, were reduced significantly. The duration of the TxA2 receptor blockade was approximately 30 and 75 min at the 1- and 2-mg/kg iv doses of the antagonist, respectively. The present data show that SQ 30741 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 due in large part to the formation of TxA2 and that discrete TxA2 receptors unrelated to receptors activated by PGD2 or PGF2 alpha are most likely located in 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
Ibrahim
I N
IN
Feng
C J
CJ
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002415:Cats; D015237:Dinoprost / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D015230:Prostaglandin D2 / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects* / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000187:drug effects* / Q000502:physiology; D017482:Receptors, Thromboxane; D012701:Serotonin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D016232:Endothelins; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D015230:Prostaglandin D2