Activation of the sodium-potassium pump contributes to insulin-induced vasodilation in humans
Tack, C.J.; Lutterman, J.A.; Vervoort, G.; Thien, T.; Smits, P.
Hypertension 28(3): 426-432
1996
ISSN/ISBN: 0194-911X PMID: 8794828 Document Number: 460588
Systemic hyperinsulinemia induces vasodilation in human skeletal muscle. This vasodilation contributes to insulin-stimulated glucose uptake and has been found to be reduced in various insulin-resistant states. The mechanism of the effect of insulin on vascular tone is not completely understood. We hypothesized that activation of the sodium-potassium pump (Na+,K+-ATPase) located in endothelial or smooth muscle cells would be involved in the insulin-mediated vasodilation. Therefore, in 24 healthy, nonsmoking, nonobese, normotensive volunteers, we infused ouabain, a specific inhibitor of Na+,K+ATPase, into the brachial artery before and during euglycemic hyperinsulinemia. As expected, insulin (systemic concentrations, approximately 700 (low) and 1400 (high) pmol cntdot L-1) induced vasodilation in the control arm (forearm blood flow (FBF, plethysmography) from 1.6+-0.2 to 2. 1+-0.4 mL cntdot dL-1 cntdot min-1 (low-insulin) and from 1.6+-0.2 to 2.1+-0.2 (high insulin), P lt .05 for both), but the increase in FBF was abolished in the ouabain-infused forearm (from 1.3+-0.1 to 1.4+-0.2 mL cntdot dL-1 cntdot min-1 (low) and from 1.3+-0.1 to 1.3+-0.1 (high), P=NS). Ouabain-induced increases in forearm potassium release were partly reversed by insulin. To investigate whether the mechanism of action could be at the endothelial level, we infused N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthase (0.05, 0.1, and 0.2 mg cntdot dL-1 cntdot min-1) intraarterially in 12 subjects and induced a clear dose-dependent decrease of FBF from 1.7+-0.2 to 1.2-0.1 mL cntdot dL-1 cntdot min-1 (P lt .01). In contrast, after ouabain (and continued insulin) infusion, L-NMMA had no effect on FBF (from 1.6+-0.4 to 1.5+-0.3 mL cntdot dL-1 cntdot min-1, n=6, P=.66). These results demonstrate that insulin induces vasodilation by stimulation of Na+,K+-ATPase. This activation of Na+,K+-ATPase could occur at the level of the endothelium rather than that of vascular smooth muscle and contributes to the endothelium-dependent vasodilator response to insulin.