Sepsis was induced in male Sprague-Dawley rats via cecal ligation and puncture. SG neurons were isolated 24 and 72 h after sepsis induction. Thereafter, the?concentration-response relationships for the Noc-stimulated NOP receptor Ca2+ current inhibition were determined using the whole-cell patch clamp technique. In addition, the Noc precursor (prepronociceptin [PNOC]) and NOP receptor messenger RNA?(mRNA) levels were determined by quantitative real-time polymerase chain reaction, and PNOC protein levels were measured by Western blot analysis.
Comparison of the Noc concentration-response relationships in SG neurons from control and septic rats 24 h after sepsis revealed similar potency and efficacy. Moreover, 72?h after sepsis, neurons from control and septic rats exhibited an increased potency compared with both groups at the 24-h time point¡ªan effect that was more pronounced in neurons from septic rats. PNOC mRNA levels were significantly greater in SG neurons isolated from septic rats compared with control neurons, but NOP receptor mRNA levels remained unchanged during the 72-h period.
Our study demonstrates the cecal ligation and puncture model-induced temporal upregulation of components within the NOP receptor signaling pathway in rat sympathetic neurons. As SG neurons provide the main sympathetic input to the heart, an increased Noc release and potency during sepsis may compromise cardiovascular function.