Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
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Involvement of Hypothalamic Periventricular GABAergic Nerves in the Central Pressor Response to Clonidine in Freely-Moving Conscious Rats
Nobuyuki HanafusaKazuaki OkamotoShingo TakatoriHiromu Kawasaki
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2012 Volume 118 Issue 3 Pages 382-390

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Abstract

Microinjection of the α2-adrenoceptor agonist clonidine into the hypothalamic periventricular nuclei (PVN) induces the pressor response associated with bradycardia in freely-moving conscious rats. This study investigated the involvement of γ-aminobutyric acid nerves (GABAergic nerves) and glutamatergic nerves in the cardiovascular response to microinjection of clonidine in the PVN. Male Wistar rats were chronically implanted with a microinjection cannula into the PVN and an arterial catheter into the abdominal aorta through the femoral artery. Blood pressure and heart rate were measured under a conscious unrestrained state. PVN injection of clonidine induced a dose-dependent pressor response concomitant with bradycardia. PVN pretreatment with GABA, muscimol (GABAA-receptor agonist), or bicuculline (GABAA-receptor antagonist) significantly inhibited the pressor response to PVN-injected clonidine without affecting bradycardia. PVN pretreatment with baclofen (GABAB-receptor agonist), 2-hydroxysaclofen (GABAB-receptor antagonist), or kynurenic acid (non-selective NMDA-type glutamate–receptor and ionotropic glutamate–receptor antagonist) did not affect the pressor response to PVN-injected clonidine. These results suggest that clonidine induces a pressor response by stimulating the presynaptic α2-adrenoceptor of GABAergic nerves in the PVN, thereby inhibiting GABAergic nerve activity.

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© The Japanese Pharmacological Society 2012
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