Reversibility of Preglomerular Active Vasoconstriction in the First Weeks after Complete Unilateral Ureteral Obstruction by Inhibition of Prostaglandin Synthesis

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Abstract
It has been 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 follow-up studies in dogs demonstrated that increased hydronephrotic vascular resistance coud be eliminated by infusion of 2-benzyl-2-imidazole, an inhibitor of thromboxane A2 synthesis. This was shown after 1 and 4 wk of complete renal obstruction. There was no such effect on vascular resistance of the contralateral, unobstructed kidney. Flow reduction and vascular resistance were not influenced by the same inhibition of prostaglandin synthesis after 8 wk of ureteral occlusion, although renal perfusion still responded to a nonspecific vasodilator, such as dopamine. Active preglomerular vasoconstriction influenced by imidazole, is present only when renal atrophy develops. Irreversible parenchymal loss, judged by renal cortical thickness, begins after 1-2 wk and is complete 6-8 wk after ureteral ligation. Once renal atrophy is established (i.e., after 8 wk or ureteral occlusion), flow reduction represents loss of renal parenchyma, not active vasoconstriction. Specificity of possible thromboxane A2 reaction in flow reduction is shown by its absence in the kidney obstructed for 5-8 h when postglomerular vasoconstriction is the cause of flow reduction (indicated by high renal pelvic pressure and intrarenal pressure). If imidazole selectively inhibits thromboxane A2 synthesis, 2 conclusions may be reached that are clinically relevant: 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.