EFFECT OF INSULIN ON ACETYLCHOLINE-INDUCED VASODILATION IN, NORMOTENSIVE SUBJECTS AND PATIENTS WITH ESSENTIAL-HYPERTENSION

Background The present study was designed to directly test the vasodil ation action of insulin and its relation to endothelium-dependent mech anisms. Methods and Results In 18 normotensive subjects and 27 patient s with untreated mild to moderate essential hypertension, we studied t he effect of intrabrachial insulin on the changes in forearm blood fla w (strain-gauge plethysmography) induced by intrabrachial acetylcholin e (at doses of 0.15, 0.45, 1.5, 4.5, and 15 mu g . min(-1) . dL(-1)), an endothelium-dependent vasodilator, or sodium nitroprusside (at dose s of 1, 2, and 4 mu g . min(-1) . dL(-1)), an endothelium-independent vasodilator. Local hyperinsulinemia (deep venous plasma insulin, 48+/- 6 and 51+/-5 mu U/mL in control subjects and hypertensive patients, re spectively) did not affect basal forearm blood flow and stimulated for earm glucose extraction (control subjects, 3+/-1% to 11+/-2%, P<.001; hypertensive patients, 3+/-1% to 6+/-1%, P<.001; P<.01 for the between -group difference). In both normotensive and hypertensive subjects, in sulin significantly potentiated acetylcholine-induced vasodilation, wh ereas it did not alter the vasodilatory response to sodium nitroprussi de. N-G-monomethyl-L-arginine, an inhibitor of endothelial nitric oxid e synthesis, blunted insulin-induced facilitation of acetyl-choline va sodilation in normotensive but not in hypertensive subjects. In contra st, in hypertensive patients but not in normotensive control subjects, the potentiation of the vascular response to acetylcholine induced by local hyperinsulinemia was abolished by intrabrachial ouabain, an inh ibitor of Na+-K+ pump. Conclusions In healthy humans and essential hyp ertensive patients alike, local physiological hyperinsulinemia per se does not increase forearm blood flow but potentiates the vasodilation induced by acetylcholine regardless of metabolic insulin resistance. T his effect is endothelium-dependent because it is not seen with nitrop russide and is related to the L-arginine-nitric oxide pathway in normo tensive subjects and to smooth muscle cell hyperpolarization in essent ial hypertensive patients.