Standley P R, Zhang F, Ram J L, Zemel M B, Sowers J R
Department of Physiology, Wayne State University, Detroit, Michigan 48201.
J Clin Invest. 1991 Oct;88(4):1230-6. doi: 10.1172/JCI115426.
Insulin attenuates the contractile responses of vascular smooth muscle (VSM) to various agonists. Insulinopenic and insulin-resistant rats lack this normal attenuation of vascular contractile responses. To study this attenuating mechanism, the effects of insulin on calcium (Ca2+) responses of cultured VSM cells (a7r5) to arginine vasopressin (AVP) and membrane potential were investigated. Insulin (1 and 100 mU/ml) shifted AVP dose-response curves to the right, reducing relative potency of AVP by 16-fold and 220-fold, respectively. Responses to AVP were significantly attenuated within 30 min of insulin application. The AVP-elicited rise in [Ca2+]i was partially dependent upon extracellular Ca2+. AVP-elicited inward current was reduced by 90 min of insulin treatment (100 mU/ml), from a peak current of -103 +/- 27 pA (normal) to -37 +/- 15 pA (insulin treated). Peak voltage-dependent Ca(2+)-dependent inward current was unaffected by insulin; however, the current-voltage curve was shifted 16 +/-3 mV to the right by insulin. Thus, insulin may reduce VSM contractile responses by attenuating agonist-mediated rises in [Ca2+]i mediated, in part, by reductions in Ca2+ influx through both receptor- and voltage-operated channels.
胰岛素可减弱血管平滑肌（VSM）对各种激动剂的收缩反应。胰岛素分泌不足和胰岛素抵抗的大鼠缺乏这种对血管收缩反应的正常减弱。为研究这种减弱机制，研究了胰岛素对培养的VSM细胞（a7r5）对精氨酸加压素（AVP）的钙（Ca2+）反应和膜电位的影响。胰岛素（1和100 mU/ml）使AVP剂量反应曲线右移，分别使AVP的相对效力降低16倍和220倍。在应用胰岛素后30分钟内，对AVP的反应显著减弱。AVP引起的细胞内Ca2+升高部分依赖于细胞外Ca2+。胰岛素处理90分钟（100 mU/ml）后，AVP引起的内向电流从峰值电流-103±27 pA（正常）降至-37±15 pA（胰岛素处理）。峰值电压依赖性Ca(2+)依赖性内向电流不受胰岛素影响；然而，电流-电压曲线因胰岛素右移16±3 mV。因此，胰岛素可能通过减弱激动剂介导的细胞内Ca2+升高来降低VSM收缩反应，这部分是通过减少通过受体和电压门控通道的Ca2+内流介导的。
