Prostaglandin B2-induced pulmonary hypertension is mediated by TxA2/PGH2 receptor stimulation.
We investigated whether the physiological effects of prostaglandin B2 (PGB2) in the pulmonary circulation might be due to stimulation of thromboxane A2-prostaglandin H2 (TxA2/PGH2) receptors. In seven anesthetized rabbits, intravenous infusion of PGB2 (5.0 micrograms/kg) caused pulmonary hypertension as evidenced by increases in right ventricular systolic blood pressure. The magnitude of the pulmonary hypertension was comparable to that observed after infusion of the TxA2 mimetic U-46619 at a significantly lower dose (0.5 micrograms/kg), indicating that the effects of PGB2 in the intact animal are similar to TxA2 but less potent. Additionally, the TxA2/PGH2-receptor antagonist SQ-29548 blocked the pulmonary blood pressure responses elicited by PGB2. Receptor-binding studies using the TxA2 receptor ligand [3H]SQ-29548 indicated that PGB2 was a potent competitor for TxA2/PGH2 receptor binding. In agreement with the results from the intact animal, however, the efficacy of inhibition with PGB2 was significantly less than that measured for the TxA2 agonist U-46619. All of these results are consistent with the hypothesis that the physiological effects of PGB2 are mediated by stimulation of TxA2/PGH2 receptors.
Department of Physiology and Cell Biology, University of Kansas, Lawrence 66045.
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000037:antagonists & inhibitors / Q000378:metabolism; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000503:physiopathology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D044262:Prostaglandin H2; D011456:Prostaglandins B; D011463:Prostaglandins H / Q000378:metabolism*; D011652:Pulmonary Circulation; D011817:Rabbits; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors / Q000502:physiology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D011456:Prostaglandins B; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044262:Prostaglandin H2; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; C042026:prostaglandin B2