Thromboxane renal effects

A direct effect of AmB on cell function was suggested by in vitro experiments, which demonstrated a vasoconstrictor action of AmB in perfused afferent arterioles and isometrically contracting rings of rabbit aorta or renal artery, effects which were prevented in Ca -free medium and by Ca" " channel blockers or theophylline [103]. Thus, AmB-induced reductions in RBF or GFR are not secondary to activation of TGF, but due to its direct vasoconstrictor effect. A role for thromboxane A2 has also been suggested based upon partial inhibition of the AmB-induced vasoconstriction and reduction in GFR by pretreatment with ibuprofen or a thromboxane receptor antagonist [104]. 

The role of arachidonate metabolites in tubular function [41,42] is more complex although the PGE compounds were shown early on to block the effect of the antidiuretic hormone (ADH) on transporting epithelia. The reason for the complexity is the effect of PGE compounds on sodium and water transport on the one hand and their effect in changing renal blood flow and intrarenal distribution on the other. It is now generally believed that the role of the vasodilator metabolites is to preserve renal homeostasis and that their effect becomes apparent when the kidney function is compromised [43]. The problem with which one is faced is to fit into this scheme the ADH-like effects of thromboxane [44] and the effects of the leukotrienes, when they are properly defined. It is possible that thromboxane and leukotrienes only become prominent in the pathological situation but this remains to be documented. 

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