Analysis of bronchoconstrictor responses to platelet-activating factor in the cat.
Bronchoconstrictor responses to platelet-activating factor (PAF) were investigated in paralyzed, anesthetized, mechanically ventilated cats. Intravenous injections of PAF caused dose-dependent increases in lung resistance (RL) and decreases in dynamic compliance (Cdyn) and systemic arterial (aortic) pressure (PAO). The increases in RL and decreases in Cdyn in response to PAF were markedly reduced by sodium meclofenamate, a cyclooxygenase inhibitor, whereas the decreases in PAO were unchanged. Increases in RL and decreases in Cdyn but not PAO in response to PAF were reduced by SQ 29,548, a thromboxane (Tx) receptor blocking agent. CV 3988, a PAF receptor antagonist, reduced bronchoconstrictor and aortic depressor responses to PAF but had no effect on responses to the Tx mimic, U 46619, or to the prostaglandin precursor, arachidonic acid. The present studies suggest that bronchoconstrictor responses but not the hypotensive response to PAF are mediated in large part by the release of arachidonic acid from cell membrane phospholipids and the formation of cyclooxygenase products including TxA2. These data indicate that although airway and vasodepressor responses to PAF in the cat are mediated by different mechanisms, a similar PAF-CV 3988-sensitive receptor is involved.
Underwood
D C
DC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Kadowitz
P J
PJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001980:Bronchi / Q000187:drug effects*; D002415:Cats; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D008469:Meclofenamic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C037913:CV 3988; C045749:SQ 29548