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Inhibition of neuronal nitric oxide synthase reduces the propofol requirements in wild-type and nNOS knockout mice.

Abstract：

BACKGROUND AND OBJECTIVE:The glutamate-nitric oxide-cyclic guanosine monophosphate pathway has been identified as a potential target for anaesthetic agents. However, mice deficient in neuronal nitric oxide synthase have a similar susceptibility to volatile anaesthetic agents to wild-type mice and are not affected by non-isoform selective inhibitors. We hypothesized that the neuronal nitric oxide synthase selective inhibitor, 7-nitroindazole, would also reduce the propofol requirements in wild-type mice but would have no effect in neuronal nitric oxide synthase knockout mice. METHODS:We determined the time to loss of righting reflex, time to painful stimulus and time to regaining the righting reflex in neuronal nitric oxide synthase knockout and wild-type mice following the intraperitoneal injection of propofol in untreated, 7-nitroindazole and vehicle only treated animals (n = 6 per group). Propofol (200 mg kg(-1)) resulted in loss of righting reflex in the untreated and vehicle only groups but was lethal in 7-nitroindazole pre-treated mice, requiring a reduced dose of propofol (100 mg kg(-1)). RESULTS:7-nitroindazole pre-treatment significantly reduced the loss of righting reflex (P < 0.001) in both wild-type and knockout mice when compared to untreated and vehicle only pre-treated animals, but had no effect on time to painful stimulus or regaining of the righting reflex. 7-nitroindazole reduced the propofol requirements in knockout mice to the same extent as in wild-type animals. CONCLUSIONS:Propofol exerts its anaesthetic effects at least partially via the glutamate-nitric oxide-cyclic guanosine monophosphate pathway. The neuronal nitric oxide synthase knockout mice are sensitive to neuronal nitric oxide synthase selective inhibition suggesting that compensatory pathways in neuronal nitric oxide synthase knockout mice exist.

journal_name

Eur J Anaesthesiol

journal_title

European journal of anaesthesiology

authors

Engelhardt T,Lowe PR,Galley HF,Webster NR

doi

10.1017/S0265021505002188

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

197-201

issue

eissn

0265-0215

issn

1365-2346

pii

S0265021505002188

journal_volume

pub_type

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Inhibition of neuronal nitric oxide synthase reduces the propofol requirements in wild-type and nNOS knockout mice.