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

被引:165
作者
TADDEI, S [1 ]
VIRDIS, A [1 ]
MATTEI, P [1 ]
NATALI, A [1 ]
FERRANNINI, E [1 ]
SALVETTI, A [1 ]
机构
[1] CNR,INST CLIN PHYSIOL,METAB UNIT,I-56100 PISA,ITALY
关键词
INSULIN; ACETYLCHOLINE; BLOOD FLOW; ENDOTHELIUM-DERIVED FACTORS;
D O I
10.1161/01.CIR.92.10.2911
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background The present study was designed to directly test the vasodilation action of insulin and its relation to endothelium-dependent mechanisms. Methods and Results In 18 normotensive subjects and 27 patients with untreated mild to moderate essential hypertension, we studied the effect of intrabrachial insulin on the changes in forearm blood flaw (strain-gauge plethysmography) induced by intrabrachial acetylcholine (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 doses 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, respectively) did not affect basal forearm blood flow and stimulated forearm 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, insulin significantly potentiated acetylcholine-induced vasodilation, whereas it did not alter the vasodilatory response to sodium nitroprusside. N-G-monomethyl-L-arginine, an inhibitor of endothelial nitric oxide synthesis, blunted insulin-induced facilitation of acetyl-choline vasodilation in normotensive but not in hypertensive subjects. In contrast, 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 inhibitor of Na+-K+ pump. Conclusions In healthy humans and essential hypertensive 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. This effect is endothelium-dependent because it is not seen with nitroprusside and is related to the L-arginine-nitric oxide pathway in normotensive subjects and to smooth muscle cell hyperpolarization in essential hypertensive patients.
引用
收藏
页码:2911 / 2918
页数:8
相关论文
共 36 条
[1]  
Ferrannini E., Buzzigoli G., Bonadonna R., Giorico M.A., Oleggini M., Graziadei L., Pedrinelli R., Brandi L., Bevilacqua S., Insulin resistance in essential hypertension, N Engl J Med, 317, pp. 350-357, (1987)
[2]  
Bonora E., Zavaroni I., Alpi O., Pezzarossa A., Bruschi F., Dall'Aglio E., Guerra L., Coscelli C., Butturini U., Relationship between blood pressure and plasma insulin in non-obese and obese non-diabetic subjects, Diabetologia, 30, pp. 719-723, (1987)
[3]  
Hall J.E., Brands M.W., Kivlighn S.D., Mizelle H.L., Hildebrandt D.A., Gaillard C.A., Chronic hyperinsulinemia and blood pressure: Interaction with catecholamines?, Hypertension, 15, pp. 519-527, (1990)
[4]  
Liang C.-S., Doherty J.U., Faillace R., Maekawa K., Arnold S., Gavras H., Hood W.B., Insulin infusion in conscious dogs: Effects on systemic and coronary hemodynamics, regional blood flows, and plasma catecholamines, J Clin Invest, 69, pp. 1321-1336, (1982)
[5]  
Anderson E.A., Hoffman R.P., Balon T.W., Sinkey C.A., Mark A.L., Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans, J Clin Invest, 87, pp. 2246-2252, (1991)
[6]  
Baron A.D., Brechtel-Hook G., Johnson A., Hardin D., Skeletal muscle blood flow: A possible link between insulin resistance and blood pressure, Hypertension, 21, pp. 129-135, (1993)
[7]  
Ferrannini E., Taddei S., Santoro D., Natali A., Boni A., Del Chiaro D., Buzzigoli G., Independent stimulation of glucose metabolism and Na<sup>+</sup>-K<sup>+</sup> exchange by insulin in the human forearm, Am J Physiol, 255, (1988)
[8]  
Natali A., Buzzigoli G., Taddei S., Santoro D., Cerri M., Pedrinelli R., Ferrannini E., Effects of insulin on hemodynamics and metabolism in human forearm, Diabetes, 39, pp. 490-500, (1990)
[9]  
Lembo G., Rendina V., Iaccarino G., Lamenza F., Volpe M., Trimarco B., Insulin reduces reflex forearm sympathetic vasoconstriction in healthy humans, Hypertension, 21, pp. 1015-1019, (1993)
[10]  
Sakai K., Imaizumi T., Masaki H., Takeshita A., Intra-arterial infusion of insulin attenuates vasoreactivity in human forearm, Hypertension, 22, pp. 67-73, (1993)