Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Springer full text link Springer
Full text links

Actions

Share

.2008 Dec;51(12):2325-32.
doi: 10.1007/s00125-008-1159-9. Epub 2008 Sep 30.

Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes

Affiliations

Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes

A Riad et al. Diabetologia.2008 Dec.

Abstract

Aims/hypothesis: Reduced bioavailability of nitric oxide (NO) is a hallmark of diabetes mellitus-induced vascular complications. In the present study we investigated whether a pharmacological increase of endothelial NO synthase (eNOS) production can restore the impaired hindlimb flow in a rat model of severe diabetes.

Methods: A model of diabetes mellitus was induced in male Sprague-Dawley rats by a single injection of streptozotozin. Rats were treated chronically with the eNOS transcription enhancer AVE3085 (10 mg [kg body weight](-1) day(-1); p.o.) or vehicle for 48 days and compared with controls. Endothelial function and arterial BP were investigated in vivo using an autoperfused hindlimb model and TIP-catheter measurement, respectively. Protein production of eNOS, total and phosphorylated vasodilator-stimulated phosphoprotein (VASP) were assessed in their quadriceps muscle tissue, whereas cyclic GMP (cGMP) concentrations were assessed in blood plasma. RNA levels of intracellular and vascular cell adhesion molecules (ICAM-1 and VCAM-1) were measured by real-time PCR.

Results: Untreated diabetic rats showed significantly reduced quadriceps muscle contents of eNOS (-64%) and phosphorylated VASP (-26%) protein associated with impaired vascular function (maximum vasodilatation: -30%, p < 0.05) and enhanced production of ICAM-1 (+121%) and VCAM-1 (+156%). Chronic treatment with AVE3085 did not alter arterial BP or severe hyperglycaemia, but did lead to significantly increased production of eNOS (+95%), cGMP (+128%) and VASP phosphorylation (+65%) as well as to improved vascular function (+36%) associated with reduced production of ICAM-1 (-36%) and VCAM-1 (-58%).

Conclusions/interpretation: In a rat model of severe diabetes, pharmacological enhancement of impaired eNOS production and NO-cGMP signalling by AVE3085 restores altered hindlimb blood flow and prevents vascular inflammation.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Biochem Biophys Res Commun. 1987 Nov 13;148(3):1482-9 - PubMed
    1. Fundam Clin Pharmacol. 2006 Dec;20(6):595-604 - PubMed
    1. Naunyn Schmiedebergs Arch Pharmacol. 1998 Jul;358(1):134-9 - PubMed
    1. Diabetologia. 2001 Nov;44(11):1973-88 - PubMed
    1. Br J Pharmacol. 2000 Jul;130(5):963-74 - PubMed

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full text links
Springer full text link Springer
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp