Clinical Investigation

Kidney International (1993) 44, 390–400; doi:10.1038/ki.1993.257

Regulation of renin-angiotensin system in unilateral ureteral obstruction

J Luis Pimentel Jr1, Manuel Martinez-Maldonado1, Josiah N Wilcox1, Susheng Wang1 and Chuying Luo1

1Atlanta Veterans Affairs Medical Center, Decatur, and Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

Correspondence: Manuel Martinez-Maldonado MD, Medical Service (111), Atlanta VA Medical Center, 1670 Clairmont Rd., Decatur, Georgia 30033, USA.

Received 13 January 1993; Revised 5 April 1993; Accepted 5 April 1993.

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Abstract

Regulation of renin-angiotensin system in unilateral ureteral obstruction. The effect of 24-hour unilateral ureteral obstruction (UUO) on the expression and regulation of the renin-angiotensin system (RAS) in rats and of pretreatment with lisinopril (5 mg/kg/day) or the AT1-R inhibitor, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lowered MAP, and normalized eicosanoid excretion by the POK. Cortex and medulla POK:CK ratio of relative density R mRNA was ~3.5 for both. Sham, POK, and CK showed renin immunoreactivity and R mRNA exclusively in juxtaglomerular position. In addition, in POK renin was expressed in mesangial cells, along greater lengths of afferent arterioles and in dilated distal tubules and loops of Henle. In situ hybridization revealed that ~20% more glomeruli in POK than CK overexpressed 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 production which, in view of the response to CEI and AT1R inhibitors, is at least partly responsible for the severe hemodynamic changes in UUO.

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