Clonidine antagonizes pressor effect of N-methyl-D-aspartate in the rostral ventrolateral medulla of rats.
The purpose of the present study was to investigate the modulatory actions of adrenoreceptor agonists on N-methyl-D-aspartate (NMDA)-induced pressor effect in rostral ventrolateral medulla (RVLM). These drugs were locally applied into RVLM of urethane-anesthetized Sprague-Dawley rats through multibarrel pipettes. Microinjection of NMDA increased the arterial pressure, an effect which was abolished by pretreatment with clonidine, whereas neither the beta-adrenergic agonist isoproterenol nor the alpha 1-adrenergic agonist phenylephrine did alter this pressor response. Previous experiments demonstrated that clonidine binds to noradrenergic alpha 2 and imidazoline receptors in the RVLM. Norepinephrine, which has high affinity for the alpha 2 receptor and low affinity to the imidazoline receptor, partially antagonized NMDA-induced hypertension. On the other hand, administration of selective imidazoline receptor antagonist idazoxan partially reversed clonidine-mediated antagonism of NMDA. Taken together, these results suggest that clonidine may modulate the excitatory amino acid-induced pressor response through noradrenergic alpha 2 and imidazoline receptors in the RVLM.
Lin
J C
JC
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Liu
D M
DM
Wang
Y
Y
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy; D054755:Imidazoline Receptors; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D008845:Microinjections; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D018690:Excitatory Amino Acid Agonists; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D010656:Phenylephrine; D016202:N-Methylaspartate; D007545:Isoproterenol; D003000:Clonidine; D009638:Norepinephrine