SEQUENTIAL-CHANGES IN RENAL EXPRESSION OF RENIN-ANGIOTENSIN SYSTEM GENES IN ACUTE UNILATERAL URETERAL OBSTRUCTION

Unilateral ureteral obstruction (UUO) alters the expression of genes e ncoding for the renin-angiotensin system (RAS). We tested the hypothes is that changes in RAS genes expression occur soon after obstruction. Indeed, measurements during the first 24 hours of UUO showed up-regula tion of renin mRNA in the obstructed kidney at 1 hour. UUO also led to increases in PRA and renal renin content, ACE activity and Ang II con centration in the experimental kidney. The obstructed kidney relative abundance of renin mRNA was increased compared to basal at 1, 2, 6, an d 24 hours; the contralateral kidney renin mRNA expression was reduced . AT(1)-R mRNA expression was diminished at 6 and 24 hours in the obst ructed kidney compared to contralateral and sham kidneys. ACE activity was upregulated in the obstructed kidney and transiently down-regulat ed in the contralateral kidney. These findings show for the first time that activation of the RAS results from as little as 1 hour of UUO an d that up-regulation of renin mRNA and ACE activity lead to increase A ng II production which down-regulates AT(1)-R mRNA as early as 6 hours post-UUO. These studies establish a pattern of sequential, differenti al regulation of the RAS genes in acute UUO that provide an explanatio n for the hemodymamic changes in this condition.