Mechanism of the cardiovascular effects of GABAB receptor activation in the nucleus tractus solitarii of the rat.
The effects of baclofen microinjected into the nucleus tractus solitarii (NTS) on blood pressure, heart rate and baroreflex bradycardia were studied in urethane-anesthetized rats. Baclofen caused dose-dependent pressor and tachycardic effects and inhibited the reflex bradycardia elicited by i.v. phenylephrine. The effects of baclofen were inhibited by similarly administered GABAB receptor antagonists, phaclofen and 2-OH-saclofen, or the non-NMDA glutamate receptor antagonist, DNQX, or by pretreatment of rats with intracisternally administered pertussis toxin. DNQX and pertussis toxin, but not the NMDA antagonist, MK-801, also inhibited baroreflex bradycardia. Intra-NTS injections of glutamate caused hypotension and bradycardia, which were potentiated by baclofen, and were not affected by either DNQX or MK-801 or by pretreatment with pertussis toxin. These findings indicate that the cardiovascular effects of stimulation of GABAB receptors in the NTS are due, at least in part, to inhibition of the depressor baroreflex response. Inhibition of the release and/or postsynaptic action of an excitatory amino acid transmitter other than glutamate is the most likely mechanism.
Florentino
A
A
Laboratory of Physiological and Pharmacological Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Varga
K
K
Kunos
G
G
D000758:Anesthesia; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D008845:Microinjections; D037342:Pertussis Toxin; D011311:Pressoreceptors / Q000187:drug effects; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D014520:Urethane; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011810:Quinoxalines; D011963:Receptors, GABA-A; D010566:Virulence Factors, Bordetella; D014520:Urethane; C056723:FG 9041; D016291:Dizocilpine Maleate; D037342:Pertussis Toxin; D001418:Baclofen; C057491:2-hydroxysaclofen