Clonidine decreases kynurenic acid production in rat brain cortex in vitro – a novel antihypertensive mechanism of action?
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Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Poland
Izabela Zakrocka   

Collegium Pathologicum, Department of Experimental and Clinical Pharmacology, Jaczewskiego 8, 20-090 Lublin, Poland
J Pre Clin Clin Res. 2016;10(1):57–59
Clonidine, an antihypertensive agent, is known to activate presynaptic α2-adrenoreceptors and imidazoline receptors in the central nervous system. Clonidine may also have influence on glutamatergic neurotransmission. Kynurenic acid (KYNA) is an endogenous antagonist of excitatory amino acid receptors. Cerebral KYNA synthesis from its bioprecursor L-kynurenine is regulated by aminotransferases localized preferentially within astrocytes. KYNA was shown to display potent neuroprotective properties. Moreover, it was reported that KYNA could reduce blood pressure levels in animal model of hypertension. The aim of the study was to discover whether the central antihypertensive agent clonidine has an influence on kynurenic acid (KYNA) production in rat brain cortex in vitro.

Material and Methods:
Cortical slices and brain cortical homogenates were incubated for 2 hours in the presence of KYNA precursor – L-kynurenine and clonidine. KYNA was separated chromatographically and detected fluorometrically.

Clonidine at the concentration of 0.001 mM – 0.1 mM did not affect KYNA production in rat brain cortex in vitro. It decreased KYNA production in rat brain cortical slices at concentrations 0.5–5 mM. Clonidine at all tested concentrations influenced neither KAT I nor KAT II activity

The study revealed that clonidine decreases KYNA production in rat brain cortex in vitro. The obtained results suggest that augmentation of glutamatergic transmission may play an important role in the antihypertensive action of clonidine.

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