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Effect of platelet activating factor of renal hemodynamics and sodium excretion
PROSTAGLANDINS
EFFECT OF PLATELET ACTIVATING FACTOR ON RENAL HEMODYNAMICS AND SCDIUM EXCRETION. Gerard E. Plante, Richard L. Hebert, Pierre Braquet, and Pierre Sirois, Department of Physiology-Pharmacology, University of Sherbrooke, Sherbrooke, Quebec, Canada, and Institut Henri Beaufour, Paris, France. Platelet activating factor (PAF) has potent hypotensive effects when administered intravenously: consequently, it is associated with profound reduction of renal blood flow (RBF), glomerular filtration (CFR) and sodium The present study was designed to examine the effects of low excretion (UNaV). doses of PAF administered directly into the renal artery, to minimize systemic Increasing doses of PAF (2, 5, 10 and 20ng/kg/min) effects of this compound. were infused successively, each during 30 minutes in the left renal artery of anesthetized dogs: 40 minutes of recovery were allowed between each dose. Minimal effects on systemic blood pressure and no influence on the contralateral kidney RBF, GFR and UNaV obtained in these studies. PAF infusion reduced UNaV by 12, 21, 37 and 60uEq/min from baseline values, at 2, 5, 10 and 20ng, respectively. Of interest, recovery of UNaV after each dose reached absolute values of increasing magnitude: 3, 48, 54 and 104uEq/min, respectively, above baseline values. No significant changes in GFR or RBF were observed in the left kidney at 2, 5 and long but a 25% fall obtained at the highest dose of PAF. When the long dose was infused together with an inhibitor of PAF receptors, under identical experimental conditions, the reduction of UNaV was abolished, but the rebound phenomenon persisted. In additional experiments, PAF was administered in successive bolus (0.15 and 0.30ug/kg) again into the left renal artery: UN,V decreased from 98 2 6 to 22 + 5, and from 145 + 11 to 53 + buEq/min, respectively; after each bolus, UNaV returned to control values within 30 minutes. In this group, GFR and RBF decreased transiently, but filtration fraction remained unchanged. Finally, the latter protocol was repeated during This prostaglandins synthesis inhibition obtained with indomethacin (3mg/kg). manoeuvre which was reported to inhibit the systemic vascular effects of PAF, failed to influence the effect of PAF on UNaV. These results indicate that PAF exerts a direct effect on the net transport of sodium by the nephron, an effect which appears to be dissociated from the small changes observed on renal hemodynamics. In addition, increasing doses of PAF not only reduced UNaV in a stepwise fashion, but was associated with a rebound natriuresis, sggesting that PAF and/or the reduction of UNaV readjusted some intrarenal humoral and/or physical equilibrium which normally maintains urinarv sodium excretion. Finallv. anti-PAF’ abolished the reduction of UN~V, secondary to the long/kg infusion’of PAF, the rebound phenomenon remaining This finding suggests that different mechanisms are probably intact. responsible for the biphasic phenomenon observed on UNaV.
OCTOBER 1985 VOL. 30 NO. 4
EFFECT OF PLATELET ACTIVATING FACTOR ON RENAL HEMODYNAMICS AND SCDIUM EXCRETION. Gerard E. Plante, Richard L. Hebert, Pierre Braquet, and Pierre Sirois, Department of Physiology-Pharmacology, University of Sherbrooke, Sherbrooke, Quebec, Canada, and Institut Henri Beaufour, Paris, France. Platelet activating factor (PAF) has potent hypotensive effects when administered intravenously: consequently, it is associated with profound reduction of renal blood flow (RBF), glomerular filtration (CFR) and sodium The present study was designed to examine the effects of low excretion (UNaV). doses of PAF administered directly into the renal artery, to minimize systemic Increasing doses of PAF (2, 5, 10 and 20ng/kg/min) effects of this compound. were infused successively, each during 30 minutes in the left renal artery of anesthetized dogs: 40 minutes of recovery were allowed between each dose. Minimal effects on systemic blood pressure and no influence on the contralateral kidney RBF, GFR and UNaV obtained in these studies. PAF infusion reduced UNaV by 12, 21, 37 and 60uEq/min from baseline values, at 2, 5, 10 and 20ng, respectively. Of interest, recovery of UNaV after each dose reached absolute values of increasing magnitude: 3, 48, 54 and 104uEq/min, respectively, above baseline values. No significant changes in GFR or RBF were observed in the left kidney at 2, 5 and long but a 25% fall obtained at the highest dose of PAF. When the long dose was infused together with an inhibitor of PAF receptors, under identical experimental conditions, the reduction of UNaV was abolished, but the rebound phenomenon persisted. In additional experiments, PAF was administered in successive bolus (0.15 and 0.30ug/kg) again into the left renal artery: UN,V decreased from 98 2 6 to 22 + 5, and from 145 + 11 to 53 + buEq/min, respectively; after each bolus, UNaV returned to control values within 30 minutes. In this group, GFR and RBF decreased transiently, but filtration fraction remained unchanged. Finally, the latter protocol was repeated during This prostaglandins synthesis inhibition obtained with indomethacin (3mg/kg). manoeuvre which was reported to inhibit the systemic vascular effects of PAF, failed to influence the effect of PAF on UNaV. These results indicate that PAF exerts a direct effect on the net transport of sodium by the nephron, an effect which appears to be dissociated from the small changes observed on renal hemodynamics. In addition, increasing doses of PAF not only reduced UNaV in a stepwise fashion, but was associated with a rebound natriuresis, sggesting that PAF and/or the reduction of UNaV readjusted some intrarenal humoral and/or physical equilibrium which normally maintains urinarv sodium excretion. Finallv. anti-PAF’ abolished the reduction of UN~V, secondary to the long/kg infusion’of PAF, the rebound phenomenon remaining This finding suggests that different mechanisms are probably intact. responsible for the biphasic phenomenon observed on UNaV.
OCTOBER 1985 VOL. 30 NO. 4