REGULATION OF RENIN-ANGIOTENSIN SYSTEM IN UNILATERAL URETERAL OBSTRUCTION

The effect of 24-hour unilateral ureteral obstruction (UUO) on the exp ression and regulation of the renin-angiotensin system (RAS) in rats a nd of pretreatment with lisinopril (5 mg/kg/day) or the AT1-R inhibito r, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lo wered MAP, and normalized eicosanoid excretion by the POK. Cortex and medulla POK:CK ratio of relative density R mRNA was approximately 3.5 for both. Sham, POK, and CK showed renin immunoreactivity and R mRNA e xclusively in juxtaglomerular position. In addition, in POK renin was expressed in mesangial cells, along greater lengths of afferent arteri oles and in dilated distal tubules and loops of Henle. In situ hybridi zation revealed that approximately 20% more glomeruli in POK than CK o verexpressed R mRNA. Blood vessels of POK consistently showed greater ACE and Ao mRNA expression than CK. Overexpression of the genes coding for members of the RAS is possibly responsible for local Ang II produ ction which, in view of the response to CEI and AT1-R inhibitors, is a t least partly responsible for the severe hemodynamic changes in UUO.