Abstract
Background: Unilateral ureteral obstruction (UUO) alters the expression of renin-angiotensin system (RAS) components and angiotensin II (Ang II) as the main arm of RAS is affected by UUO. Objectives: In this study the role of Ang II subtypes 1 and 2 receptors (AT1R and AT2R) antagonists (losartan and PD123319) was examined in renal hemodynamic responses to graded Ang II infusion in sham, 3-day UUO and removal UUO (RUUO) models in rats. Materials and Methods: Seventy-one male Wistar rats randomly divided into three different sets of animal models; sham-operated, UUO and RUUO that each set contains three groups treated with vehicle, losartan, and PD123319. Renal vascular responses to Ang II infusion were measured at controlled renal perfusion pressure (RPP). Results: The graded Ang II infusion decreased renal blood flow (RBF), increased renal vascular resistance (RVR) and mean arterial pressure (MAP) in vehicle or PD123319 treated groups significantly (P<0.005), but no significant difference was found between these treated groups. However, RBF, RVR and MAP responses to graded Ang II infusion in losartan-treated rats were attenuated significantly when compared with vehicle or PD123319 treated groups (P<0.05). In addition, the RBF, RVR and MAP responses to Ang II were not similar in sham, UUO and RUUO rats treated with losartan. Conclusions: Vascular responses to Ang II in UUO and RUUO rat model treated with losartan is not as the normal pattern.
Highlights
Unilateral ureteral obstruction (UUO) alters the expression of renin-angiotensin system (RAS) components and angiotensin II (Ang II) as the main arm of RAS is affected by UUO
Baseline measurements No significant differences were detected in terms of mean arterial pressure (MAP), renal blood flow (RBF), renal perfusion pressure (RPP), and renal vascular resistance (RVR) between the groups in each set of animal models in control or equilibrium period before infusion of vehicle or antagonists (Figure 1: A-L)
Effect of vehicle or antagonists The results showed that vehicle infusion had no significant effect on the MAP, RPP, RBF, and RVR between the groups in each set of animal models 30 min post vehicle infusion (Figure 1; A-L)
Summary
Unilateral ureteral obstruction (UUO) alters the expression of renin-angiotensin system (RAS) components and angiotensin II (Ang II) as the main arm of RAS is affected by UUO. Results: The graded Ang II infusion decreased renal blood flow (RBF), increased renal vascular resistance (RVR) and mean arterial pressure (MAP) in vehicle or PD123319 treated groups significantly (P < 0.005), but no significant difference was found between these treated groups. RBF, RVR and MAP responses to graded Ang II infusion in losartan-treated rats were attenuated significantly when compared with vehicle or PD123319 treated groups (P < 0.05). Unilateral ureteral obstruction (UUO) is an important model of progressive renal disease characterized by renal hemodynamic impairment [1]. UUO decreases the renal blood flow (RBF) and increases the renal vascular resistance (RVR) [4] progressively in ipsilateral kidney until the UUO is removed, while UUO removal (RUUO) can prevent the complications of acute UUO [5].
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