Sequential changes in renal expression of renin-angiotensin system genes in acute unilateral ureteral obstruction

Unilateral ureteral obstruction (UUO) alters the expression of genes encoding for the renin-angiotensin system (RAS). We tested the hypothesis that changes in RAS genes expression occur soon after obstruction. Indeed, measurements during the first 24 hours of UUO showed up-regulation 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 concentration in the experimental kidney. The obstructed kidney relative abundance of renin mRNA was increased compared to basal at 1, 2, 6, and 24 hours; the contralateral kidney renin mRNA expression was reduced. AT1-R mRNA expression was diminished at 6 and 24 hours in the obstructed kidney compared to contralateral and sham kidneys. ACE activity was up-regulated in the obstructed kidney and transiently down-regulated 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 and that up-regulation of renin mRNA and ACE activity lead to increase Ang II production which down-regulates AT1-R mRNA as early as 6 hours post-UUO. These studies establish a pattern of sequential, differential regulation of the RAS genes in acute UUO that provide an explanation for the hemodynamic changes in this condition.