Hasdai D, Holmes D R, Richardson D M, Izhar U, Lerman A
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Cardiovasc Res. 1998 Sep;39(3):644-50. doi: 10.1016/s0008-6363(98)00144-8.
To examine the hypothesis that insulin and insulin-like growth factor I (IGF-I) attenuate endothelin-induced contraction of porcine coronary epicardial arteries in vitro.
Endothelin-induced coronary vasoconstriction is mediated by two types of receptors, A (ETA) and B (ETB), resulting in calcium influx. Both insulin and IGF-I attenuate endothelin-induced calcium influx into porcine coronary artery smooth muscle.
Epicardial arteries harvested from juvenile pigs were contracted with cumulative concentrations of endothelin-1 (ETA- and ETB-receptor agonist; 10(-10)-10(-6) M) or of sarafotoxin-6c (ETB-receptor agonist; 10(-11)-10(-7) M). In additional experiments, endothelin-1 or sarafotoxin-6c were added after incubation with 10(-8) M regular insulin or IGF-I. These experiments were repeated in vessels without endothelium. Contraction for each vessel was calculated relative to the response to 60 mM KCl.
The maximal contractions to endothelin-1 in vessels with and without endothelium were 158 +/- 8 and 200 +/- 21%, respectively (p < 0.05 at 10(-8.5)-10(-6.5) M). Both insulin (at 10(-7)-10(-6) M) and IGF-I (at 10(-6.5)-10(-6) M) attenuated the contraction to endothelin-1 in vessels with intact endothelium, as well as in vessels without endothelium (at 10(-7) and 10(-6) M for insulin and 10(-7.5)-10(-6) M for IGF-I). The maximal contractions to sarafotoxin-6c in vessels with and without endothelium were 54 +/- 13 and 84 +/- 7%, respectively (p < 0.05 at 10(-9), 10(-8.5) and 10(-7) M). Insulin and IGF-I did not affect the response to sarafotoxin-6c in vessels with and without endothelium.
Insulin and IGF-I attenuated ETA-receptor-mediated coronary contraction through an endothelium-independent mechanism. The IGF axis may serve as an endogenous modulator of endothelin-mediated vasoconstriction.
检验胰岛素和胰岛素样生长因子I（IGF-I）在体外减弱内皮素诱导的猪冠状动脉心外膜动脉收缩这一假说。
内皮素诱导的冠状动脉血管收缩由两种受体介导，即A（ETA）和B（ETB）受体，会导致钙内流。胰岛素和IGF-I均可减弱内皮素诱导的钙流入猪冠状动脉平滑肌。
从幼年猪获取的心外膜动脉用累积浓度的内皮素-1（ETA和ETB受体激动剂；10⁻¹⁰ - 10⁻⁶ M）或蛙皮毒素-6c（ETB受体激动剂；10⁻¹¹ - 10⁻⁷ M）使其收缩。在另外的实验中，在与10⁻⁸ M常规胰岛素或IGF-I孵育后加入内皮素-1或蛙皮毒素-6c。这些实验在无内皮的血管中重复进行。计算每根血管的收缩相对于对60 mM氯化钾反应的情况。
有内皮和无内皮血管对内皮素-1的最大收缩分别为158±8%和200±21%（在10⁻⁸.⁵ - 10⁻⁶.⁵ M时p<0.05）。胰岛素（在10⁻⁷ - 10⁻⁶ M）和IGF-I（在10⁻⁶.⁵ - 10⁻⁶ M）均可减弱有完整内皮血管以及无内皮血管（胰岛素在10⁻⁷和10⁻⁶ M，IGF-I在10⁻⁷.⁵ - 10⁻⁶ M）对内皮素-1的收缩。有内皮和无内皮血管对蛙皮毒素-6c的最大收缩分别为54±13%和84±7%（在10⁻⁹、10⁻⁸.⁵和10⁻⁷ M时p<0.05）。胰岛素和IGF-I不影响有内皮和无内皮血管对蛙皮毒素-6c的反应。
胰岛素和IGF-I通过非内皮依赖机制减弱ETA受体介导的冠状动脉收缩。IGF轴可能作为内皮素介导血管收缩的内源性调节剂。
