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  • Title: Hemodynamic effects of PAF-acether on the dog kidney.
    Author: Hébert RL, Sirois P, Braquet P, Plante GE.
    Journal: Prostaglandins Leukot Med; 1987 Mar; 26(3):189-202. PubMed ID: 3033688.
    Abstract:
    PAF-Acether (PAF) is a potent vasodilator produced in several organs, including the kidney. In the present study, the effect of intra-femoral PAF (0.78 micrograms/kg) in control dogs (Group 1) or indomethacin (3 mg/kg) treated animals (Group 2) was examined. In Group 1, systemic blood pressure dropped from 108 +/- 8 to 47 +/- 7 mmHg following PAF and hematocrit rose from 42 +/- 2 to 56 +/- 2%. These changes were associated with a reduction in both urine flow, urinary sodium (from 69 +/- 9 to 25 +/- 6 muEq/min), glomerular filtration and renal plasma flow (from 28 +/- 2 to 11 +/- 1 and 52 +/- 5 to 26 +/- 4 ml/min, respectively). All parameters returned to normalcy during the following 50 minutes. In Group 2, the systemic effects of PAF were abolished by indomethacin. However, indomethacin failed to prevent the renal abnormalities which were altered as in Group 1. In additional experiments (Group 3) the influence of BN-52021, a specific antagonist of PAF receptors, was examined. The dose of PAF utilized in this group was 0.78 micrograms/kg, whereas BN-52021 was administered 30 minutes before PAF injections in increasing doses (1.0, 2.5, 5.0 and 25.0 micrograms). This antagonist blocked the effect of PAF on blood pressure and renal parameters in a dose-related manner. Finally, the effect of intrarenal PAF was studied (Group 4: increasing continuous infusions of 2, 5, 10, and 20 ng/kg/min; Group 5: single bolus of 0.15 and 0.30 micrograms/kg). In these two groups, the systemic effects of PAF were abolished as expected. In Group 4, a dose related reduction of urinary sodium was observed during the continuous infusion of PAF. Only at higher doses, was an effect on glomerular filtration and renal plasma flow observed. In Group 5, a marked reduction of urinary sodium (from 110 +/- 15 to 22 +/- 5 muEq/min) occurred while glomerular filtration and renal plasma flow decreased by approximately 50%. These data support a direct influence of PAF on urinary sodium excretion and renal hemodynamics. The peripheral effects of this compound are mediated by vasodilatory prostaglandins, as shown in Group 2. Finally, the actions of this powerful vasodilator on the kidney do not require the intervention of systemic influences, as clearly demonstrated in Groups 4 and 5.
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