Activation of the Sodium-Potassium Pump Contributes to Insulin-Induced Vasodilation in Humans

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 28; no. 3; pp. 426 - 432
• Main Authors: Tack, Cees J.J, Lutterman, Jos A, Vervoort, Gerald, Thien, Theo, Smits, Paul
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01-09-1996; Hagerstown, MD Lippincott
• Subjects: Adolescent; Adult; Biological and medical sciences; Blood vessels and receptors; Dose-Response Relationship, Drug; Forearm - blood supply; Fundamental and applied biological sciences. Psychology; Glucose - metabolism; Glucose Clamp Technique; Humans; Insulin - pharmacology; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Ouabain - pharmacology; Regional Blood Flow - drug effects; Sodium-Potassium-Exchanging ATPase - metabolism; Vascular Resistance - drug effects; Vasodilation - drug effects; Vasodilation - physiology; Vertebrates: cardiovascular system; Human; Pancreatic hormone; Endothelial cell; Enzyme; Smooth muscle; Activation; K; Insulin; Vasodilation; Endothelium; Protein hormone; Vasomotricity; Na; Blood vessel; Hydrolases; exchanging ATPase; Circulatory system; Biological effect; Mechanism of action
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.hyp.28.3.426

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 [centered dot] L ()) induced vasodilation in the control arm (forearm blood flow [FBF, plethysmography] from 1.6 plus/minus 0.2 to 2.1 plus/minus 0.4 mL [centered dot] dL [centered dot] min [low insulin] and from 1.6 plus/minus 0.2 to 2.1 plus/minus 0.2 [high insulin], P < .05 for both), but the increase in FBF was abolished in the ouabain-infused forearm (from 1.3 plus/minus 0.1 to 1.4 plus/minus 0.2 mL [centered dot] dL [centered dot] min [low] and from 1.3 plus/minus 0.1 to 1.3 plus/minus 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 -monomethyl-L-arginine (L-NMMA), an inhibitor of endothelial nitric oxide synthase (0.05, 0.1, and 0.2 mg [centered dot] dL [centered dot] min ()) intra-arterially in 12 subjects and induced a clear dose-dependent decrease of FBF from 1.7 plus/minus 0.2 to 1.2 plus/minus 0.1 mL [centered dot] dL [centered dot] min (P < .01). In contrast, after ouabain (and continued insulin) infusion, L-NMMA had no effect on FBF (from 1.6 plus/minus 0.4 to 1.5 plus/minus 0.3 mL [centered dot] dL [centered dot] min, 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. (Hypertension. 1996;28:426-432.)