Inhibition of platelet-activating factor induced renal hemodynamic and tubular dysfunctions with L-655,240, a new thromboxane-prostaglandin endoperoxide antagonist.
The continuous infusion or bolus injection of the platelet-activating factor (PAF) is associated with profound hypotension, marked reductions of renal plasma flow, glomerular filtration, and urinary sodium excretion. All these effects are inhibited by blocking PAF receptors. To examine further the potential mediators of PAF on renal function, we utilized L-655,240 (6 mg/kg, intravenously), a thromboxane-prostaglandin endoperoxide antagonist, to study the systemic and renal response to PAF (0.8 micrograms/kg, intravenously) in the anesthetized dog, using clearance methodology. PAF decreased blood pressure from 115 +/- 7 to 54 +/- 4 mmHg (1 mmHg = 133.3 Pa), renal plasma flow from 105 +/- 6 to 74 +/- 56 mL/min, and glomerular filtration from 43 +/- 3 to 32 +/- 1 mL/min. PAF also reduced urine volume from 1.1 +/- 0.2 to 0.4 +/- 0.1 mL/min, and urinary sodium from 158 +/- 7 to 86 +/- 7 mu equiv./min. L-655,240 alone had no significant effect on blood pressure, renal plasma flow, and filtration rate, at any dose. However, the 6-mg/kg dose resulted in a slight elevation of diuresis, from 1.1 +/- 0.2 to 1.9 +/- 0.1 mL/min, and urinary sodium, from 134 +/- 13 to 212 +/- 19 mu equiv./min. All doses of L-655,240 blocked the effect of PAF on blood pressure. However, the two lower doses of this antagonist (1 and 3 mg/kg) failed to prevent the PAF-induced fall of renal plasma flow and filtration rate, and attenuated the effect on urinary sodium in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Hébert
R L
RL
Department of Physiology, University of Sherbrooke, Qué., Canada.
Sirois
P
P
Plante
G E
GE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D009318:Natriuresis / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012016:Reference Values; D012079:Renal Circulation / Q000187:drug effects*; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D007211:Indoles; D010972:Platelet Activating Factor; D013931:Thromboxanes; C052517:L 655240