A defect of lipopolysaccharide-induced nitric oxide synthase gene expression in the paraventricular nucleus of Lewis rats

The hypothalamo-pituitary-adrenal (HPA) axis activity of Lewis rats has bee n reported to be hyporesponsive to immune challenge, and nitric oxide (NO) has been demonstrated to be involved in the regulation of the HPA axis duri ng the response to immune challenge. The present study investigates the eff ect of systemic injection of Lipopolysaccharide (LPS) on NO production with in the paraventricular nucleus (PVN) of immature female Fisher-344 (F344) a nd Lew/N rats (Lew/N), to clarify the pathophysiological role of NO in the dysregulation of the HPA axis in Lewis/N. Intraperitoneal injection of 25 m g/kg LPS significantly increased neuronal NO synthase (nNOS) mRNA expressio n in the PVN of F344 rats, but did not change nNOS mRNA levels in the PVN o f Lew/N rats. CRF mRNA levels in the PVN significantly increased in respons e to LPS injection only in F344 rats. In contrast, inducible NOS (iNOS) mRN A increased similarly in both strains. These results demonstrated a defect of up-regulation of nNOS gene expression in the PVN of Lew/N rats following immune challenge. The defect appears to be associated with the dysfunction of the HPA axis in this strain. An increase in iNOS mRNA may partially res tore NO production in the PVN.