Involvement of platelet activating factor and thromboxane A2 in the renal response to unilateral ureteral obstruction.
Platelet activating factor (PAF) and thromboxane A2 (TxA2) are two vasoactive mediators which can decrease renal blood flow. Both are synthesized by various intrarenal cell types or by macrophages which may infiltrate the kidney during unilateral ureteral obstruction (UUO). In several experimental systems, PAF receptor activation is accompanied by TxA2 release; pharmacological modification of TxA2 synthesis or receptor activation modulates the response to PAF. The involvement of PAF in UUO has not been studied previously, and the role of TxA2 has not been clearly defined by previous investigations. The hemodynamic response to acute UUO is characterized by decreases in renal blood flow (RBF) and glomerular filtration rate and an acute increase in ureteral pressure. In the present experiments, the involvement of either PAF or TxA2 in the acute response to UUO was studied by determining if blockade of either the TxA2 or PAF receptor would affect the renal hemodynamic response to UUO. In addition, the effect of blockade of the TxA2 receptor on the renal response to PAF was determined. Our results indicate that only a small portion of the renal response to PAF is mediated by TxA2, and that neither PAF nor TxA2 can be implicated in the acute hemodynamic response to UUO. TxA2 or PAF involvement in the chronic response to UUO still remains to be determined.
Felsen
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D
James Buchanan Brady Foundation, Division of Urology, New York Hospital Cornell Medical Center, New York.
Loo
M H
MH
Marion
D N
DN
Vaughan
E D
ED
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004285:Dogs; D005231:Fatty Acids, Unsaturated; D005260:Female; D006834:Hydrazines / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D011312:Pressure; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000187:drug effects; D017482:Receptors, Thromboxane; D012079:Renal Circulation / Q000187:drug effects; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D014513:Ureter / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D010972:Platelet Activating Factor; D011450:Prostaglandin Endoperoxides, Synthetic; D011806:Quinolinium Compounds; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C050531:SRI 63-441; D013928:Thromboxane A2; C045749:SQ 29548