[Insulin mitigates the effect of free fatty acid to cause endothelial dysfunction in rat aortic rings]
Yerong Yu1, Jinsu Zhu, Yonggang Wu
1Department of Endocrinology and Metabolism, The First University Hospital, West China University of Medical Sciences, Chengdu 610041, China.
Objective:
To investigate whether free fatty acid (FFA) directly and independently causes endothelial dysfunction and whether enhancing insulin action mitigates FFA-induced endothelial dysfunction.
Methods:
Twenty-nine S-D rats were divided into 4 groups and infused by jugular catheterization with different solutions: 20% intralipid + heparin (0.72 IU/min) for 4 hours (FFA group, n = 9), short-acting insulin by hyperinsulinemic euglycemic clamp for 4 hours (Ins group, n = 5), intralipid + heparin and insulin by hyperinsulinemic euglycemic clamp for 4 hours (Ins + FFA group, n = 10), and normal saline (18 microliter/min) for 4 hours(C group, n = 5). After the infusion, the rats were killed and their aortic rings were resected and put into organ bath and connected to a force transducer and amplifier. PGF2a was added into the organ bath to constrict the rings until the constriction tension reached a balance. Then acethylcholine (Ach) and sodium nitroprusside (SNP) of increasing concentrations were added to relax the rings to record the endothelial dependent vasodilatation (EDV) and endothelium independent vasodilatation (EIV).
Results:
The EDV value was 85.0% +/- 3.2% in C group and 54.8% +/- 2.5% in FFA group (C vs FFA, P = 0.002); 80.6% +/- 1.8% in Ins group (C vs Ins, P = ns); 72.8% +/- 2.1% in Ins + FFA group (FFA + Ins vs C P = 0.02, FFA + Ins vs FFA, P = 0.005). The EIV response in the three experimental groups was not different from that in the control group.
Conclusion:
FFA damages the endothelisal dependant vasodilatation of aorta, thus causing endothelial dysfunction by direct interaction with the endothelium. FFA may be proatherogenic. Hyperinsulinemia has salutary effects on endothelial function in the context of elevated FFA.
