RGD Reference Report - Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats. - Rat Genome Database

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Selective resistance to vasoactive effects of insulin in muscle resistance arteries of obese Zucker (fa/fa) rats.

Authors: Eringa, EC  Stehouwer, CD  Roos, MH  Westerhof, N  Sipkema, P 
Citation: Eringa EC, etal., Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1134-9. Epub 2007 Jul 10.
RGD ID: 2292133
Pubmed: PMID:17623751   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00516.2006   (Journal Full-text)

Obesity is related to insulin resistance and hypertension, but the underlying mechanisms are unclear. Insulin exerts both vasodilator and vasoconstrictor effects on muscle resistance arteries, which may be differentially impaired in obesity. OBJECTIVES: To investigate whether vasodilator and vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats and the roles of Akt and endothelial NO synthase (eNOS). METHODS/RESULTS: Effects of insulin were studied in resistance arteries isolated from cremaster muscles of lean and obese Zucker rats. In arteries of lean rats, insulin increased activity of both NO and endothelin (ET-1), resulting in a neutral effect under basal conditions. In arteries of obese rats, insulin induced endothelin-mediated vasoconstriction (-15 +/- 5% at 1 nM, P < 0.05 vs. lean). Insulin induced vasodilatation during endothelin receptor blockade in arteries of lean rats (20 +/- 5% at 1 nM) but not in those of obese rats. Inhibition of NO synthesis increased vascular tone (by 12 +/- 2%) and shifted insulin-mediated vasoreactivity to vasoconstriction (-25 +/- 1% at 1 nM) in lean rats but had no effect in arteries of obese rats, indicating reduced NO activity. Protein analysis of resistance arteries revealed that insulin-mediated activation of Akt was preserved in obese rats, whereas expression of eNOS was markedly decreased. CONCLUSIONS: Vasodilator but not vasoconstrictor effects of insulin are impaired in muscle resistance arteries of obese rats, and this selective impairment is associated with decreased protein levels of eNOS. These findings provide a new mechanism linking obesity to insulin resistance and hypertension.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
obesity  ISONos3 (Rattus norvegicus)2292133; 2292133protein:decreased expression:arteryRGD 
obesity  IEP 2292133protein:decreased expression:arteryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information