ACTIVATION OF THE SODIUM-POTASSIUM PUMP CONTRIBUTES TO INSULIN-INDUCED VASODILATION IN HUMANS

Systemic hyperinsulinemia induces vasodilation in human skeletal muscl e. This vasodilation contributes to insulin-stimulated glucose uptake and has been Found to br reduced in various insulin-resistant stales. The mechanism of the effect of insulin on vascular tone is not complet ely understood. We hypothesized that activation of the sodium-potassiu m pump (Na+,K+-ATPase) located in endothelial or smooth muscle cells w ould be involved in the insulin-mediated vasodilation, Therefore, in 2 4, healthy, nonsmoking, nonobese, normotensive volunteers, we infused ouabain, a specific inhibitor of Na+,K+-ATPase, into the brachial arte ry before and during euglycemic hyperinsulinemia. As expected, insulin (systemic concentrations, approximately 700 [low] and 1400 [high] pmo l . L(-1)) induced vasodilation in the control arm (forearm blood flow [FBF, plethysmography] from 1.6 +/- 0.2 to 2.1 +/- 0.4 mL . dL(-1). m in(-1) [low insulin] and from 1.6 +/- 0.2 to 2.1 +/- 0.2 [high insulin ], P < .05 for both), but the increase in FBF was abolished in the oua bain-infused forearm (from 1.3 +/- 0.1 to 1.4 +/- 0.2 mL . dL(-1). min (-1) [low] and from 1.3 +/- 0.1 to 1.3 +/- 0.1 [high], P = NS). Ouabai n-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 . dL(-1). min(-1)) intra-arterially in 12 subjects and induced a c lear dose-dependent decrease of FBF from 1.7 +/- 0.2 to 1.2 +/- 0.1 mL . dL(-1). min(-1) (P < .01). In contrast, after ouabain (and continue d insulin) infusion, L-NMMA had no effect on FBF (from 1.6 +/- 0.4 to 1.5 +/- 0.3 mL . dL(-1). min(-1), n = 6, P = .66), These results demon strate that insulin induces vasodilation by stimulation of Na+,K+-ATPa se. This activation of Na+,K+-ATPase could occur at the level of the e ndothelium rather than that of vascular smooth muscle and contributes to the endothelium-dependent vasodilator response to insulin.