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Am J Physiol. 1993 Jul;265(1 Pt 2):F96-103.

Effects of rC5a on the circulation of normal and split hydronephrotic rat kidneys.

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1
I. Institute of Physiology, University of Heidelberg, Germany.

Abstract

Systemic release of complement-derived anaphylatoxin C5a is suggested to be involved in the pathogenesis of renal failure during endotoxic or severe traumatic shock. In the present study we analyzed renal hemodynamic effects of recombinant human complement 5a (rC5a) and examined whether these effects are mediated by the secondary release of other inflammatory mediators. Intravenous infusion of rC5a (0.5 micrograms/min) in thiobarbital-anesthetized rats decreased renal blood flow (RBF) by 20 and 34% after 20 and 60 min, respectively. Glomerular filtration rate (GFR) was reduced by 45%, whereas filtration fraction and blood pressure were not significantly changed by rC5a. Hematocrit (Hct) increased by 11%, whereas white blood cell count decreased by 40%. Renal rC5a effects were completely inhibited by the competitive leukotriene D4/E4 antagonist ICI-198615, whereas the competitive thromboxane A2 (TxA2) antagonist daltroban only partly reversed rC5a effects on RBF and GFR. The competitive platelet-activating factor (PAF) antagonist L-695989 did not influence renal or systemic rC5a effects. These results point to an rC5a-mediated synthesis and release of cysteinyl leukotrienes and TxA2, whereas PAF does not seem to be released after intravenous rC5a in rats. To determine the cellular source of cysteinyl-leukotriene synthesis, rats were depleted of polymorphonuclear cells (PMN) by intraperitoneal injection of anti-rat PMN antibodies, which abrogated renal and systemic hemodynamic rC5a effects, suggesting that PMN participate in the synthesis and release of cysteinyl leukotrienes. The exact localization of renovascular rC5a effects was performed on the model of the split hydronephrotic rat kidney.(ABSTRACT TRUNCATED AT 250 WORDS).

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