Document Detail


Chronic hypertension enhances presynaptic inhibition by baclofen in the nucleus of the solitary tract.
MedLine Citation:
PMID:  20038748     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The selective gamma-aminobutyric acid B-subtype receptor agonist baclofen activates both presynaptic and postsynaptic receptors in the brain. Microinjection of baclofen into the nucleus of the solitary tract increases arterial pressure, heart rate, and sympathetic nerve discharge consistent with inhibition of the arterial baroreflex. The magnitude of these responses is enhanced in hypertension and is associated with increased postsynaptic GABA(B) receptor function. We tested whether a presynaptic mechanism contributes to the enhanced baclofen inhibition in hypertension. Whole-cell recordings of second-order baroreceptor neurons, identified by 4-(4-(dihexadecylamino)styryl)-N-methylpyridinium iodide labeling of aortic nerve, were obtained in brainstem slices from normotensive control and renal-wrap hypertensive rats. After 4 weeks, arterial blood pressure was 162+/-9 mm Hg in hypertensive (n=6) and 107+/-3 mm Hg in control rats (n=6/11; P<0.001). Baclofen reduced the amplitude of excitatory postsynaptic currents evoked by solitary tract stimulation and the EC(50) of this inhibition was greater in control (1.5+/-0.5 micromol/L; n=6) than in hypertensive cells (0.6+/-0.1 micromol/L; n=9; P<0.05). Baclofen (1 micromol/L) elicited greater inhibition on evoked response in hypertensive (58+/-6%; n=9) than in control cells (40+/-6%; n=8; P<0.05). Another index of presynaptic inhibition, the paired-pulse ratio (ratio of second to first evoked response amplitudes at stimulus intervals of 40 ms), was greater in hypertensive (0.60+/-0.08; n=8) than in control cells (0.48+/-0.06; n=5; P<0.05). The results suggest that in renal-wrap hypertensive rats, baclofen causes an enhanced presynaptic inhibition of glutamate release from baroreceptor afferent terminals to second-order neurons in the nucleus of the solitary tract. This enhanced presynaptic inhibition could contribute to altered baroreflex function in hypertension.
Authors:
Weirong Zhang; Steve Mifflin
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2009-12-28
Journal Detail:
Title:  Hypertension     Volume:  55     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-21     Completed Date:  2010-02-22     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, Tex 76107, USA. wzhang@hsc.unt.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Baclofen / pharmacology*
Baroreflex / drug effects,  physiology
Chronic Disease
Disease Models, Animal
GABA Agonists / pharmacology*
Glutamic Acid / metabolism
Hypertension / physiopathology*
Male
Neurons / drug effects,  physiology
Pressoreceptors / drug effects
Presynaptic Terminals / drug effects,  physiology
Probability
Random Allocation
Rats
Rats, Sprague-Dawley
Reference Values
Solitary Nucleus / drug effects*
Synaptic Potentials / drug effects
Synaptic Transmission / drug effects*
Grant Support
ID/Acronym/Agency:
HL-56637/HL/NHLBI NIH HHS; R01 HL056637-09/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/GABA Agonists; 1134-47-0/Baclofen; 56-86-0/Glutamic Acid
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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