Is nitric oxide involved as a mediator of cerebrovascular changes in the early phase of experimental pneumococcal meningitis?
Nitric oxide (NO) is a mediator of haemodynamic changes and cytotoxicity in in vivo models of inflammation such as endotoxaemic shock. The purpose of this study was to investigate whether NO may be involved in the increase of cerebral blood flow (CBF), intracranial pressure (ICP) and brain water content, known to occur in the early phase of pneumococcal meningitis. Rats injected intracisternally with live pneumococci were either untreated or received 5 mg kg-1 i.v. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase. Pretreatment with L-NAME prevented the increase in CBF, ICP and brain water content, as seen in untreated animals. CBF tended to return towards baseline when rats were treated with L-NAME 2 h after pneumococcal injection. Whereas none of the untreated and L-NAME-pretreated animals died during the 6 h observation period, 3 out of 9 rats treated with L-NAME and 7 out of 9 rats with simultaneous i.v. injection of L-NAME and L-arginine died. Our results provide preliminary evidence that NO may be involved as a mediator of CBF changes and oedema formation in the early phase of pneumococcal meningitis in the rat. NO inhibition, however, may have detrimental effects of still unidentified cause, as indicated by the increased mortality in treated animals. Further studies with analysis of the causes of mortality, structurally different NO synthase inhibitors and direct evaluation of NO synthase induction are needed to further support this hypothesis.
Haberl
R L
RL
Department of Neurology, University of Munich, Germany.
Anneser
F
F
Ködel
U
U
Pfister
H W
HW
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000627:therapeutic use; D001834:Body Water / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000502:physiology*; D007427:Intracranial Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D008586:Meningitis, Pneumococcal / Q000188:drug therapy / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester