Objective: Carperitide, alpha-human atrial natriuretic peptide, is used in expectation of protecting the kidney during sepsis in internal care unit; however, the detailed mechanism of action has not been clarified yet. As septic acute kidney injury (AKI) does not induce characteristic histological damage, we aimed assess the effects of carperitide treatment on the decline of renal function during lipopolysaccharide-induced AKI by using real-time intravital imaging technique. Design and Method: The renal function was analyzed by the bolus-shot FITC-inulin kinetics method that visualizes the tubular flow after free filtration from glomeruli. Results: Both tubular flow and urine flow from bladder remarkably slowed down in LPS-treated rats in prior to the onset of hypotension and acidosis. The reduction of tubular flow was induced by the retention of the injected FITC-inulin at proximal tubules and, therefore, the tubular flow in the downstream nephron was markedly decreased, even at the phase in which both blood pressure and glomerular filtration were maintained. Fluid resuscitation improved the decreased tubular flow rate only in a part of nephron, displaying heterogeneity on the effect, although the urine flow rate from bladder was almost normalized. On the other hand, carperitide ubiquitously increased the tubular flow rate with normalizing urine flow from bladder. Conclusions: Carperitide improved the urine flow rate in the proximal tubules that are resistant to the fluid resuscitation in rat endotoxemic model.
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