Henrion D, Laher I
Institut national de la santé et de la recherche médicale U 141, Hôpital Lariboisière, Paris, France.
Can J Physiol Pharmacol. 1994 Aug;72(8):849-54. doi: 10.1139/y94-120.
Insulin might play a role in the hypertension occurring in insulin-resistant diabetes. In addition, insulin has recently been shown to potentiate norepinephrine (NE) induced vascular tone. We used ring segments of the rabbit facial artery mounted in a myograph to test the hypothesis that potentiation of NE-induced tone by insulin may be related to activation of protein kinase C (PKC) and tyrosine kinase (TK). NE-induced contractions in the presence of insulin (1 mU/mL) were 200% (NE 0.1 and 0.3 microM), 252% (NE 1 microM), and 129% (NE 3 microM) of control. Insulin (1 mU/mL) had no effect on NE (10 and 100 microM) induced contractions. The potentiation by insulin of NE-induced tone was not altered by endothelium removal and could be mimicked by phorbol-12-myristate-13-acetate (PMA, 0.1 microM). Histamine-induced contractions were not altered by insulin (1 mU/mL). Insulin potentiation of NE-induced tone was suppressed by pretreatment of the rabbit facial artery with the PKC inhibitor calphostin C (0.1 microM) or the TK inhibitor genistein (10 microM). 45Ca2+ influx due to NE (3 microM) did not change in the presence of insulin (1 mU/mL) or PMA (0.1 microM) despite a higher contractile response, so that wall force per unit of 45Ca2+ influx was increased by insulin (1 mU/mL) and PMA (0.1 microM). Calphostin C (0.1 microM) and genistein (10 microM) both prevented the increase in wall force per unit of 45Ca2+ influx due to insulin (1 mU/mL). Our study shows that insulin potentiates NE-induced tone through a TK- and PKC-dependent mechanism.
胰岛素可能在胰岛素抵抗性糖尿病所致高血压中发挥作用。此外，最近有研究表明胰岛素可增强去甲肾上腺素（NE）诱导的血管张力。我们使用安装在肌张力测定仪中的兔面动脉环段来检验以下假设：胰岛素增强NE诱导的张力可能与蛋白激酶C（PKC）和酪氨酸激酶（TK）的激活有关。在存在胰岛素（1 mU/mL）的情况下，NE诱导的收缩分别为对照组的200%（NE 0.1和0.3 μM）、252%（NE 1 μM）和129%（NE 3 μM）。胰岛素（1 mU/mL）对NE（10和100 μM）诱导的收缩无影响。胰岛素对NE诱导张力的增强作用不受内皮去除的影响，且可被佛波醇-12-肉豆蔻酸酯-13-乙酸酯（PMA，0.1 μM）模拟。组胺诱导的收缩不受胰岛素（1 mU/mL）影响。兔面动脉预先用PKC抑制剂钙泊三醇C（0.1 μM）或TK抑制剂染料木黄酮（10 μM）处理后，胰岛素对NE诱导张力的增强作用受到抑制。尽管收缩反应增强，但在存在胰岛素（1 mU/mL）或PMA（0.1 μM）的情况下，由NE（3 μM）引起的45Ca2+内流并未改变，因此胰岛素（1 mU/mL）和PMA（0.1 μM）使每单位45Ca2+内流产生的壁力增加。钙泊三醇C（0.1 μM）和染料木黄酮（10 μM）均能阻止胰岛素（1 mU/mL）引起的每单位45Ca2+内流壁力的增加。我们的研究表明，胰岛素通过依赖TK和PKC的机制增强NE诱导的张力。
