Prolonged inhibition of brain nitric oxide synthase by short-term systemic administration of nitro-L-arginine methyl ester.

Abstract:

:We studied the dose-response characteristics and the temporal profile of inhibition of brain nitric oxide (NO) synthase (NOS) elicited by i.v. administration of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). L-NAME was administered i.v. in awake rats equipped with a venous cannula. L-NAME was injected in cumulative doses of 5, 10, 20 and 40 mg/kg and rats were sacrificed 30 min after the last dose. NOS catalytic activity was assayed in forebrain cytosol as the conversion of [3H]L-arginine into [3H]L-citrulline. L-NAME attenuated brain NOS activity in a dose-dependent manner but enzyme activity could not be inhibited by more than approximately 50%. After a single 20 mg/kg injection of L-NAME the inhibition of brain NOS activity was time dependent and reached a stable level at 2 hrs (52% of vehicle). Inhibition after a single injection was still present at 96 hrs, albeit to a lower magnitude. We conclude that intravenous administration of L-NAME in rats at concentrations commonly used in physiological experiments leads to a dose and time-dependent but partial inhibition of brain NOS catalytic activity. The finding that the inhibition persists for several days after a single administration is consistent with the hypothesis that nitro-L-arginine, the active principle of L-NAME, binds to NOS irreversibly.

journal_name

Neurochem Res

journal_title

Neurochemical research

authors

Iadecola C,Xu X,Zhang F,Hu J,el-Fakahany EE

doi

10.1007/BF00967330

subject

Has Abstract

pub_date

1994-04-01 00:00:00

pages

501-5

issue

4

eissn

0364-3190

issn

1573-6903

journal_volume

19

pub_type

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