title: Differential roles of iNOS and nNOS at rostral ventrolateral medulla during experimental endotoxemia in the rat.
abstract: We investigated the differential contribution of inducible and neuronal nitric oxide synthase (iNOS and nNOS) at the rostral ventrolateral medulla (RVLM) to endotoxemia induced by E. coli lipopolysaccharide (LPS). In Sprague-Dawley rats maintained under propofol anesthesia, i.v. administration of LPS (15, 30, or 45 mg/kg) induced a reduction (phase I), followed by an augmentation (phase II) and a secondary decrease (phase III) in the power density 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 mRNA exhibited a significant surge that began with phase I endotoxemia, reaching progressively its peak at phase III. Discernible down-regulation of nNOS mRNA was not detected until the last phase of endotoxemia. Pretreatment with microinjection of the selective iNOS inhibitor, aminoguanidine (250 pmol), into the bilateral RVLM significantly prolonged phases II and III endotoxemia, blunted the initial and secondary hypotension, and antagonized the upregulation of iNOS mRNA. Similar pretreatment with the selective nNOS inhibitor, 7-nitroindazole (1 pmol), on the other hand, discernibly shortened phase II and prolonged phase III endotoxemia, and induced progressive hypotension by antagonizing the rebound increase in SAP. We conclude that the relative prevalence of functional expression and molecular synthesis of iNOS over nNOS in the RVLM may be a crucial determinant for the reduction or loss in power density of the vasomotor components of SAP signals during experimental endotoxemia.
authors.affiliation: Department of Medical Education and Research, Veterans General Hospital-Kaohsiung, Taiwan, Republic of China.
authors.forename: J Y
authors.initials: JY
authors.lastname: Chan
authors.forename: S H
authors.initials: SH
authors.lastname: Wang
authors.forename: S H
authors.initials: SH
authors.lastname: Chan
mesh_terms: D000818:Animals; D001794:Blood Pressure; D019446:Endotoxemia / Q000378:metabolism* / Q000401:mortality; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli; D006146:Guanidines / Q000494:pharmacology; D007022:Hypotension / Q000209:etiology; D007191:Indazoles / Q000494:pharmacology; D008070:Lipopolysaccharides; D008297:Male; D008526:Medulla Oblongata / Q000201:enzymology*; D008845:Microinjections; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014666:Vasomotor System / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; C004479:pimagedine; C080122:7-nitroindazole