Exendin-4 Improves Impaired Endothelial Dependent Vasodilation in Obese Rat

HAN Li-na, YU Ye-rong, WANG Ben

Abstract

To determine whether exendin-4 (Ex-4)might improve endothelial dysfunction in aorta isolated from high-fatty diet induced obese rats. Methods 20 male Wistar rats were divided into normal control and high-fat supplement (OB) groups (n=10 for each group). The rats were sacrificed after 10 weeks feeding and thoracic aorta was dissected and cut into four rings of 3 mm length, the response to acethylcholine (Ach) and sodium nitroprusside (SNP) were examined in organ bath containing Krebs-Henseleit (K-H) solution. In order to study the direct effects of Ex-4 on obese rats vascular function, the aortic rings obtained from obese rats were incubated with K-H solution (OB-C group, n=10),or with K-H solution plus Ex-4 (OB-Ex group, n=10). Aortic rings obtained from normal control group (n=10) were incubated with K-H solution. After 1 hour of incubation, the aortic rings were precontracted with norepinephrine (0.1 μmol/L), then the rings were exposed to cumulative concentration of Ach (10-9-10-4 mol/L)or sodium SNP (10-10-10-6 mol/L) to test the endothelial dependent (EDV) and independent vasodilation (EIV). The blood plasma of the rats was collected for biochemical test and celiac fat and body mass data were also obtained. Results The levels of serum triglyceride, total cholesterol, and free fat acid were elevated in the obese group compared with that of normal control group (P<0.01). The ratio of celiac fat and body mass in the obese rats was also higher than the control (P<0.05). Ach caused a concentration dependent vascular relaxation in all pre-constricted aortic rings. Compared to the control group, maximal endothelium dependent relaxation in the obese group was impaired (P<0.05). The EIV values were comparable between two groups. Pre-incubation of obese rat's vessels with Ex-4 significantly increased cumulative relaxation to Ach (P<0.05). SNP induced vessels relaxation had no statistical significance each groups (P>0.05). Conclusion Endothelial function was impaired in obese rats. Ex-4 directly mitigates impaired endothelial-dependent vasorelaxation of isolated obese rat's aortas.

 

Keywords: Obese, Glucagon-like peptide-1, Exendin-4, Endothelial dependent vasodilation

 

Full Text:

PDF


References


Dean field J, Donald A, Ferri C, et al. Endothelial function and dysfunction. Part I : Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and endothelial factors of the european society of hypertension. J Hypertens, 2005; 23 (1); 7-17.

Holst JJ, Donald A. Ferri C, et al. Regulation of glucagon secretion by incretins. Diabetes Obes Metab.2011; 13(Suppl 1): 89-94.

Nystrom T, Gutniak MK. Zhang Q. et al. Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab.2004 ;287(6); El209-1215.

Deng G, Long Y. Yu YR, et al. Adiponectin directly improves endothelial dysfunction in obese rats through the AMPK-eNOS Pathway. Int J Obes ( Lond) ,2010;34( 1); 165-171.

Montero D, Walther G, Perez-Martin A, et al. Endothelial dysfunction, inflammation, and oxidative stress in obese children and adolescents: markers and effect of lifestyle intervention. Obes Rev,2011; 19(6); 1279-1283.

Kobayasi R, Akamine EH, Davel AP, et al. Oxidative stress and inflammatory mediators contribute to endothelial dysfunction in high-fat diet-induced obesity in mice. J Hypertens, 2010; 28(10): 2111-2119.

Mudaliar S, Henry RR. Incretin therapies; effects beyond gl у cemic control. Eur J Intern Med, 2009; 20 (Suppl 2):S319- 328.

Basu A, Charkoudian N, Schrage W. et al. Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab,2007 ;293(5) :E1289-1295.

Dozier КС, Cureton EL, Kwan RO, et al. Glucagon-like peptide-1 protects mesenteric endothelium from injury during inflammation. Peptides,2009;30(9): 1735-1741.

Goyal S, Kumar S, Bijjem KV, et al. Role of glucagon-like peptide-1 in vascular endothelial dysfunction. Indian J Exp Biol, 2010 ?48( 1):61-69.


Refbacks

  • There are currently no refbacks.