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Cardiovascular actions of leptin in the subfornical organ are abolished by diet induced obesity.
MedLine Citation:
PMID:  22103447     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The subfornical organ (SFO), a sensory circumventricular organ lacking the normal blood brain barrier with well documented roles in cardiovascular regulation, has recently been identified as a potential site at which the adipokine, leptin, may act to influence central autonomic pathways. Systemic and central leptin administration has been shown to increase blood pressure and it has been suggested that selective leptin resistance contributes to obesity related hypertension. Given the relationship between obesity and hypertension, the present study was undertaken to investigate the cardiovascular consequences of direct administration of leptin into the SFO of young lean rats and in the diet induced obesity (DIO) rat model which has been shown to be leptin resistant. Leptin administration (500 fmol) directly into the SFO of young rats resulted in rapid decreases in blood pressure (BP) (mean area under the curve (AUC) = -677.8 ± 167.1 mmHg*sec, n=9), without an effect on HR (mean AUC = -21.2±13.4 beats, n=9), effects which were dose related as microinjection of 5 pmol leptin into the SFO had a larger effect on BP (mean AUC = -972.3±280.1 mmHg*sec, n=4). These BP effects were also shown to be site specific as leptin microinjection into non-SFO regions or into the ventricle was without effect on BP (non SFO: mean AUC = -22.4 ± 55.3 mmHg*sec, n=4; ventricle: mean AUC = 194.0 ± 173.0 mmHg*sec, n=6). In contrast, microinjection of leptin into leptin resistant DIO rats was without effect on BP (mean AUC = 205.2±75.1 mmHg*sec, n=4). These observations suggest that the SFO may be an important relay center through which leptin, in normal weight, leptin responsive rats, acts to maintain BP within normal physiological limits through descending autonomic pathways involved in cardiovascular control and that in obese, leptin-resistant, rats leptin no longer influences SFO neurons resulting in elevated BP, thus contributing to obesity related hypertension.
Authors:
Pauline M Smith; Alastair V Ferguson
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-21
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal of Neuroendocrinology © 2011 Blackwell Publishing.
Affiliation:
Dept. Physiology, Queen's University Kingston ON Canada, K7L 3L6.
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