7-Nitroindazole inhibits pial arteriolar vasodilation in a rat model of pneumococcal meningitis.
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.
Paul
R
R
Department of Neurology, Ludwig-Maximilians-University of Munich, Klinikum Grosshadern, Germany.
Koedel
U
U
Pfister
H W
HW
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*
D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole