title: 7-Nitroindazole inhibits pial arteriolar vasodilation in a rat model of pneumococcal meningitis.
abstract: This study investigates how the neuronal and inducible nitric oxide synthase (NOS) pathways contribute to the cerebrovascular changes in the early phase of experimental pneumococcal meningitis in rats. Using a closed cranial window preparation, the diameters of pial arterioles were measured during 4 hours after intracisternal injection of heat-killed pneumococci and compared with controls (n = 6). Injection of pneumococci (n = 7) caused a significant increase in pial arteriolar diameter (157 +/- 22% after 4 hours; P < 0.05, compared with 104 +/- 11% in controls), intracranial pressure, CSF white blood cell counts, and brain water content. Treatment with the neuronal NOS inhibitor 7-nitroindazole (50 mg/kg given intraperitoneally, n = 5) prevented pneumococci-induced vasodilation (107 +/- 20% at 4 hours), whereas S-methylisothiourea (SMT; 0.1 mg/kg given intraperitoneally, n = 5), which predominantly inhibits the inducible NOS, did not influence pneumococci-induced vasodilation (154 +/- 38% at 4 hours). S-methylisothiourea at a dose of 1.0 mg/kg (n = 5), attenuated the vasodilation (124 +/- 18% at 4 hours). However, the increase in mean arterial blood pressure after SMT at 1.0 mg/kg, but not at 0.1 mg/kg, suggests that the higher dose of SMT influenced the constitutive NOS activity, causing inhibition of the pneumococci-induced vasodilation. Neither SMT (at both doses) nor 7-nitroindazole influenced the increase in brain water content, intracranial pressure, and CSF white blood cell counts in pneumococci-challenged rats. Our study suggests that pial arteriolar vasodilation in the early phase of experimental pneumococcal meningitis is mediated by the neuronal NOS pathway.
authors.affiliation: Department of Neurology, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Paul
authors.forename: U
authors.initials: U
authors.lastname: Koedel
authors.forename: H W
authors.initials: HW
authors.lastname: Pfister
mesh_terms: D000818:Animals; D001158:Arteries / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D008586:Meningitis, Pneumococcal / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole