Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat

We investigated the differential contribution of inducible and neuronal nit ric oxide synthase (iNOS and nNOS) at the rostral ventrolateral medulla (RV LM) to endotoxemia induced by E. coil lipopolysaccharide (LPS). In Sprague- Dawley rats maintained under propofol anesthesia, i.v. administration of LP S (15, 30, or 45 mg/kg) induced a reduction (phase I), followed by an augme ntation (phase II) and a secondary decrease (phase III) in the power densit y of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP ) signals. LPS also induced an immediate hypotension, followed by a rebound increase and a secondary decrease in SAP. In addition, the level of iNOS m RNA exhibited a significant surge that began with phase I endotoxemia, reac hing progressively its peak at phase III. Discernible down-regulation of nN OS mRNA was not detected until the last phase of endotoxemia. Pretreatment with microinjection of the selective iNOS inhibitor, aminoguanidine (250 pm ol), into the bilateral RVLM significantly prolonged phases II and III endo toxemia, blunted the initial and secondary hypotension, and antagonized the upregulation of iNOS mRNA. Similar pretreatment with the selective nNOS in hibitor, 7-nitroindazole (1 pmol), on the other hand, discernibly shortened phase II and prolonged phase III endotoxemia, and induced progressive hypo tension by antagonizing the rebound increase in SAP. We conclude that the r elative prevalence of functional expression and molecular synthesis of iNOS over nNOS in the RVLM may be a crucial determinant for the reduction or lo ss in power density of the vasomotor components of SAP signals during exper imental endotoxemia.