Document Detail


Leptin impairs cardiovagal baroreflex function at the level of the solitary tract nucleus.
MedLine Citation:
PMID:  19770402     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Circulating leptin is elevated in some forms of obesity-related hypertension, associated with impaired baroreflex function. Leptin receptors are present on vagal afferent fibers and neurons within the solitary tract nucleus, providing an anatomic distribution consistent with baroreflex modulation. Although solitary tract nucleus microinjection of 144 fmol/60 nL of leptin had no significant effect on baroreflex sensitivity for control of the heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats, 500 fmol of leptin impaired baroreflex sensitivity for bradycardia in response to increases in pressure (1.15+/-0.04 versus 0.52+/-0.12 ms/mm Hg; P<0.01). Transgenic ASrAOGEN rats with low brain angiotensinogen have an upregulation of the leptin receptor and p85 alpha mRNA in the dorsal medulla relative to Sprague-Dawley rats. Consistent with these observations, the response to leptin was enhanced in ASrAOGEN rats, because both the 144-fmol (1.46+/-0.08 versus 0.75+/-0.10 ms/mm Hg; P<0.001) and 500-fmol (1.36+/-0.32 versus 0.44+/-0.06 ms/mm Hg; P<0.05) leptin microinjections impaired baroreflex sensitivity. At these doses, leptin microinjection had no effect on resting pressure, heart rate, or the tachycardic response to decreases in pressure in Sprague-Dawley or ASrAOGEN rats. Thus, exogenous leptin at sites within the solitary tract nucleus impairs the baroreflex sensitivity for bradycardia induced by increases in arterial pressure, consistent with a permissive role in mediating increases in arterial pressure. Baroreflex inhibition was enhanced in animals with evidence of increased leptin receptor and relevant signaling pathway mRNA.
Authors:
Amy C Arnold; Hossam A Shaltout; Patricia E Gallagher; Debra I Diz
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-21
Journal Detail:
Title:  Hypertension     Volume:  54     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-22     Completed Date:  2009-11-12     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1001-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Baroreflex / drug effects*,  physiology*
Bradycardia / metabolism,  physiopathology
Disease Models, Animal
Heart Rate / drug effects*,  physiology
Leptin / adverse effects,  metabolism*,  pharmacology*
Male
Microinjections
Probability
RNA, Messenger / analysis
Random Allocation
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Reference Values
Sensitivity and Specificity
Solitary Nucleus / drug effects*,  physiology
Sympathetic Nervous System / drug effects,  physiology
Grant Support
ID/Acronym/Agency:
HL-51952/HL/NHLBI NIH HHS; P01 HL051952/HL/NHLBI NIH HHS; P01 HL051952-150002/HL/NHLBI NIH HHS; P01 HL051952-168199/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Leptin; 0/RNA, Messenger
Comments/Corrections

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


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