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Anesthesiology. 2011 Feb;114(2):374-9. doi: 10.1097/ALN.0b013e318204e029.

Salvinorin A produces cerebrovasodilation through activation of nitric oxide synthase, κ receptor, and adenosine triphosphate-sensitive potassium channel.

Author information

  • 1Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China.

Abstract

BACKGROUND:

Salvinorin A is a nonopioid, selective κ opioid-receptor agonist. Despite its high potential for clinical application, its pharmacologic profile is not well known. In the current study, we hypothesized that salvinorin A dilates pial arteries via activation of nitric oxide synthase, adenosine triphosphate-sensitive potassium channels, and opioid receptors.

METHODS:

Cerebral artery diameters and cyclic guanosine monophosphate in cortical periarachnoid cerebrospinal fluid were monitored in piglets equipped with closed cranial windows. Observation took place before and after salvinorin A administration in the presence or absence of an opioid antagonist (naloxone), a κ opioid receptor-selective antagonist (norbinaltorphimine), nitric oxide synthase inhibitors (N(G)-nitro-L-arginine and 7-nitroindazole), a dopamine receptor D2 antagonist (sulpiride), and adenosine triphosphate-sensitive potassium and Ca-activated K channel antagonists (glibenclamide and iberiotoxin). The effects of salvinorin A on the constricted cerebral artery induced by hypocarbia and endothelin were investigated. Data were analyzed by repeated measures ANOVA (n = 5) with statistical significance set at a P value of less than 0.05.

RESULTS:

Salvinorin A induced immediate but brief vasodilatation that was sustained for 30 min via continual administration every 2 min. Vasodilatation and the associated cyclic guanosine monophosphate elevation in cerebrospinal fluid were abolished by preadministration N(G)-nitro-L-arginine, but not 7-nitroindazole. Although naloxone, norbinaltorphimine, and glibenclamide abolished salvinorin A-induced cerebrovasodilation, this response was unchanged by iberiotoxin and sulpiride. Hypocarbia and endothelin-constricted pial arteries responded similarly to salvinorin A, to the extent observed under resting tone.

CONCLUSIONS:

Salvinorin A dilates cerebral arteries via activation of nitric oxide synthase, adenosine triphosphate-sensitive potassium channel, and the κ opioid receptor.

PMID:
21245734
[PubMed - indexed for MEDLINE]
PMCID:
PMC3387285
Free PMC Article

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