Acute Urinary Bladder Distension Triggers ICAM-1-mediated Renal Oxidative Injury via the Norepinephrine–renin–angiotensin II System in Rats

Background/PurposeAcute urinary bladder distension (AUBD) can activate bladder mechanical afferent and renal sympathetic nerves, which contributes to renal vasoconstriction. We hypothesized that AUBD-induced renal sympathetic activation may contribute to inflammatory responses and end-organ damage via activation of angiotensin-II-receptor-mediated intercellular adhesion molecule-1 (ICAM-1) expression and leukocyte infiltration in the kidney.MethodsWe evaluated the effect of 2 hours of AUBD induced by a threshold volume (micturition volume) on renal oxygen tension, microcirculation, renal reactive oxygen species (ROS) and monocyte/ macrophage (ED-1) infiltration, and ICAM-1 expression in the kidneys of urethane-anesthetized female Wistar rats. Bilateral ureteral dissection, renal denervation and intrarenal angiotensin II type 1 receptor blockade (2 mg/kg valsartan) were used to determine their roles in AUBD-induced renal oxidative stress.ResultsOur results showed that AUBD evoked hypertension, a reduction in cortex oxygen tension and microcirculation, and increased renal ROS production, which were caused by increased perivascular and interstitial monocyte/macrophage infiltration and endothelial ICAM-1 overexpression. Renal denervation and angiotensin II type 1 receptor antagonist, but not bilateral ureter dissection, abolished the reduction in cortex oxygen tension and microcirculation, increased renal ROS production, increased perivascular monocyte/macrophage infiltration, and led to endothelial ICAM-1 overexpression in the kidney.ConclusionAcute urinary retention enhances renal sympathetic activity, which causes renal vasoconstriction and increases oxidative stress, adhesion-molecule expression and leukocyte infiltration in the rat kidney via the angiotensin II type 1 receptor pathway.