Effects of Lipopolysaccharide on Inflammation within the Bladder Muscle and Muscle Contractility in the Rats / 대한비뇨기과학회지

ABSTRACT

PURPOSE: The mechanisms, which alter urinary bladder muscle function during infectious cystitis, are poorly understood. The objective of this study was to identify potential resident targets for endotoxin lipopolysaccharide(LPS) within normal bladder smooth muscle and test the hypothesis that LPS induces an inflammatory response within the bladder muscle and that this is associated with a decrease in muscle contractility. MATERIALS AND METHODS: Male rats were studied 24 hours after a single bolus i.p. injection of LPS(15mg/kg). Whole-mount preparations of the bladder muscle were immunohistochemically stained for neutrophils(myeloperoxidase), macrophages(ED2), activated leukocytes(LFA-1) and mast cells(FITC-Avidin). Contractile activity was assessed from muscle strips of the bladder in response to bethanechol(0.3-300microM). Voiding frequency and urine volume for 24 hours were measured using metabolic cage. Cystometry was performed to measure the intravesical bladder pressure. RESULTS: Using the resident macrophage marker ED2, dense network of macrophages were observed within the bladder muscle of control and LPS treated rats. Few neutrophils(myeloperoxidase-positive cells, 2.3 +/- 0.38 cells, x200) were detected in whole-mounts of bladder muscle of control rats, while LPS pretreatment resulted in a significant increase in the number of neutrophils which demonstrate inflammatory response(10.8 +/- 1.70 cells, x200, p<0.001). LFA-1 immunohistochemistry demonstrated an increased presence of LFA-1 positive cells in bladder muscle of LPS treated rats, which had a morphology similar to both neutrophils and resident macrophages. The expression of LFA-1 is known as a marker of cells that are in an activated state. LPS pretreatment resulted in a significant reduction in bladder muscle contractions in response to bethanechol(i.e. control = 0.049 +/- 0.010 vs. LPS= 0.029 +/- 0.003 gr/mm2/sec, 100microM, p<0.05). Voiding frequency of LPS treated rats was significantly increased compared to that of control rats. In LPS treated rats, voiding phase representing bladder contractility in cystometry was observed. CONCLUSIONS: These data demonstrate that a single intraperitoneal injection of LPS initiates an inflammatory response within the bladder muscle that is associated with a decrease in the functional activity of the bladder. We hypothesize that secretions from the resident macrophages and extravasated leukocytes within the muscle cause the observed suppression in bladder muscle activity in vitro.