Reversibility of preglomerular active vasoconstriction in the first weeks after complete unilateral ureteral obstruction by inhibition of prostaglandin synthesis.

In previous studies our group has shown that unilateral complete ureteral ligation is followed by flow reduction, which clearly precedes renal atrophy and contributes to hydronephrotic renal cortical damage by ischemia. Long-term followup studies in dogs have demonstrated that increased hydronephrotic vascular resistance could be eliminated by infusion of 2-benzyl-2-imidazole, an inhibitor of thromboxane A2 synthesis. This was shown after 1 and 4 weeks of complete renal obstruction, and there was no such effect on the vascular resistance of the contralateral, unobstructed kidney. Flow reduction and vascular resistance were not influenced by the same inhibition of prostaglandin synthesis after 8 weeks of ureteral occlusion, although renal perfusion still responded to a nonspecific vasodilator, such as dopamine. Thus, active preglomerular vasoconstriction, influenced by imidazole, is present only when renal atrophy develops. Irreversible parenchymal loss, judged by renal cortical thickness, begins after 1 to 2 weeks and is complete 6 to 8 weeks after ureteral ligation. Once renal atrophy is established (that is, after 8 weeks of ureteral occlusion), flow reduction represents loss of renal parenchyma, and not active vasoconstriction. The specificity of the possible thromboxane A2 reaction in flow reduction is shown by its absence in the kidney that has been obstructed for 5 to 8 hours when postglomerular vasoconstriction is the cause of flow reduction (indicated by high renal pelvic pressure and intrarenal pressure). If we accept that imidazole selectively inhibits thromboxane A2 synthesis, we reach 2 conclusions that are clinically relevant: 1) thromboxane A2-mediated active vasoconstriction is 1 factor in the pathophysiology of hydronephrotic atrophy, and 2) the presence of thromboxane A2-mediated active vasoconstriction indicates when hydronephrotic atrophy develops and (more importantly) when it is still reversible, with respect to renal function. These findings can be used as a physiologic basis of a clinical test to predict reversibility of hydronephrotic damage.