Involvement of hypothalamic periventricular GABAergic nerves in the central pressor response to clonidine in freely-moving conscious rats.

Abstract

Microinjection of the α(2)-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 (GABA(A)-receptor agonist), or bicuculline (GABA(A)-receptor antagonist) significantly inhibited the pressor response to PVN-injected clonidine without affecting bradycardia. PVN pretreatment with baclofen (GABA(B)-receptor agonist), 2-hydroxysaclofen (GABA(B)-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 α(2)-adrenoceptor of GABAergic nerves in the PVN, thereby inhibiting GABAergic nerve activity.

• Authors: Nobuyuki Hanafusa, Kazuaki Okamoto, Shingo Takatori, Hiromu Kawasaki
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 118 Issue 3 Pg. 382-90 ( 2012) ISSN: 1347-8648 [Electronic] Japan
• PMID: 22450196 (Publication Type: Journal Article)

Chemical References

• Antihypertensive Agents
• Excitatory Amino Acid Antagonists
• GABA Agents
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• GABA-B Receptor Agonists
• GABA-B Receptor Antagonists
• Receptors, Glutamate
• Muscimol
• gamma-Aminobutyric Acid
• Kynurenic Acid
• Baclofen
• Clonidine
• 2-hydroxysaclofen
• Bicuculline

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Baclofen (analogs & derivatives, pharmacology)
• Bicuculline (pharmacology)
• Blood Pressure (drug effects, physiology)
• Clonidine (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• GABA Agents (pharmacology)
• GABA-A Receptor Agonists (pharmacology)
• GABA-A Receptor Antagonists (pharmacology)
• GABA-B Receptor Agonists (pharmacology)
• GABA-B Receptor Antagonists (pharmacology)
• GABAergic Neurons (drug effects, physiology)
• Heart Rate (drug effects)
• Hypothalamus
• Kynurenic Acid (pharmacology)
• Male
• Muscimol (pharmacology)
• Paraventricular Hypothalamic Nucleus (drug effects, physiology)
• Rats
• Rats, Wistar
• Receptors, Glutamate (physiology)
• gamma-Aminobutyric Acid (pharmacology)