De Ciuceis Carolina, Rizzoni Damiano, Porteri Enzo, Boari Gianluca E M, Zani Francesca, Miclini Marco, Tiberio Guido A M, Giulini Stefano M, Paiardi Silvia, Rizzardi Nicola, Platto Caterina, Agabiti-Rosei Enrico
Clinica Medica, Department of Medical and Surgical Sciences, University of Brescia, Brescia, Italy.
J Vasc Res. 2008;45(6):512-20. doi: 10.1159/000128604. Epub 2008 May 2.
The effect of insulin on the vasoconstriction induced by norepinephrine is at present controversial. We have previously demonstrated that high-concentration insulin may induce an increased reactivity to norepinephrine in mesenteric small resistance arteries of spontaneously hypertensive rats. The aim of the present study was to evaluate the effects of low- and high-concentration insulin on the concentration-response curves to norepinephrine and acetylcholine in subcutaneous small resistance arteries of hypertensive and diabetic patients. Twelve normotensive subjects (NT), 11 patients with essential hypertension (EH), 8 patients with non-insulin-dependent diabetes mellitus (NIDDM), and 8 patients with both EH and NIDDM (EH + NIDDM) were included in the study. Subcutaneous small resistance arteries were dissected and mounted on an isometric myograph. Concentration-response curves to norepinephrine (from 10(-8) to 10(-5) mol/l) and acetylcholine (from 10(-9) to 10(-5) mol/l) were performed in the presence or absence of insulin 715 pmol/l (low concentration) and 715 nmol/l (high concentration). A significant reduction in the contractile response to norepinephrine was observed in NT after preincubation of the vessels with both low- and high-concentration insulin. No reduction was observed in NIDDM and EH + NIDDM, while a significant decrease was obtained in EH with high-concentration insulin. Moreover, a significant difference in reduction in contractile response at maximal concentration of norepinephrine in the presence of low-concentration insulin was observed in NT compared to EH (p = 0.03), NIDDM (p = 0.02), and EH + NIDDM (p = 0.05), whereas no difference was observed with high-concentration insulin. No differences in the concentration-response curves to acetylcholine before or after precontraction with either low- or high-concentration insulin were observed in any group. In conclusion, insulin at low (physiological) concentrations seems to induce a decreased reactivity to norepinephrine in subcutaneous small resistance arteries of NT, but this effect was lost in EH, NIDDM and EH + NIDDM. This effect does not seem to involve acetylcholine-stimulated nitric oxide release.
胰岛素对去甲肾上腺素诱导的血管收缩的影响目前存在争议。我们之前已经证明，高浓度胰岛素可能会使自发性高血压大鼠肠系膜小阻力动脉对去甲肾上腺素的反应性增加。本研究的目的是评估低浓度和高浓度胰岛素对高血压和糖尿病患者皮下小阻力动脉中去甲肾上腺素和乙酰胆碱浓度-反应曲线的影响。该研究纳入了12名血压正常的受试者（NT）、11名原发性高血压患者（EH）、8名非胰岛素依赖型糖尿病患者（NIDDM）和8名同时患有EH和NIDDM的患者（EH + NIDDM）。解剖皮下小阻力动脉并将其安装在等长肌动描记器上。在存在或不存在715 pmol/l（低浓度）和715 nmol/l（高浓度）胰岛素的情况下，进行对去甲肾上腺素（从10^(-8)至10^(-5) mol/l）和乙酰胆碱（从10^(-9)至10^(-5) mol/l）的浓度-反应曲线实验。在用低浓度和高浓度胰岛素预孵育血管后，NT组中观察到对去甲肾上腺素的收缩反应显著降低。在NIDDM组和EH + NIDDM组中未观察到降低，而在EH组中高浓度胰岛素使其显著降低。此外，与EH组（p = 0.03）、NIDDM组（p = 0.02）和EH + NIDDM组（p = 0.05）相比，在NT组中，存在低浓度胰岛素时，在去甲肾上腺素最大浓度下收缩反应降低存在显著差异，而高浓度胰岛素时未观察到差异。在任何组中，在用低浓度或高浓度胰岛素预收缩前后，对乙酰胆碱的浓度-反应曲线均未观察到差异。总之，低（生理）浓度的胰岛素似乎会使NT组皮下小阻力动脉对去甲肾上腺素的反应性降低，但这种效应在EH组、NIDDM组和EH + NIDDM组中消失。这种效应似乎不涉及乙酰胆碱刺激的一氧化氮释放。
