甲状腺激素对大鼠骨骼肌阻力动脉的直接血管舒缩作用。

The direct vasomotor effect of thyroid hormones on rat skeletal muscle resistance arteries.

作者信息

Park K W, Dai H B, Ojamaa K, Lowenstein E, Klein I, Sellke F W

机构信息

Department of Anesthesia & Critical Care, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.

出版信息

Anesth Analg. 1997 Oct;85(4):734-8. doi: 10.1097/00000539-199710000-00005.

DOI:10.1097/00000539-199710000-00005

PMID:9322448

Abstract

UNLABELLED

The present study examines the hypothesis that the hormones have direct vasodilatory effects and attempts to determine whether the effects are endothelium-dependent. Rat skeletal muscle resistance arteries of approximately 100 microns were dissected, and vessel diameter changes were monitored using a videodetection system. After equilibration at 37 degrees C, each vessel was preconstricted with the thromboxane analog U46619 1 microM, and the percentage of dilation was measured after exposure to increasing concentrations of triiodothyronine (T3) or levothyroxine (T4) (10(-10) to 10(-7) M). Dilation in response to T3 was also measured after endothelial denudation and pretreatment with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) 10 microM, the cyclooxygenase inhibitor indomethacin 10 microM, the adenosine triphosphate-sensitive K+ channel blocker glibenclamide 1 microM, or the beta-adrenergic antagonist propranolol 1 microM. Both T3 and T4 demonstrated concentration-dependent dilation of the U46619-preconstricted vessels (P < 0.001 each), with T3 having a greater effect than T4 (P < 0.05) (36% +/- 9% [mean +/- SD] dilation at 10(-7) M T3 vs 24% +/- 6% dilation at 10(-7) M T4). In comparison, isoproterenol 10(-7) M produced 56% +/- 6% dilation. T3-mediated vasodilation was attenuated but not abolished by endothelial denudation (18% +/- 3% dilation at 10(-7) M T3) (P < 0.01), L-NNA (15% +/- 7% dilation at 10(-7) M T3) (P < 0.01), indomethacin (20% +/- 9% dilation at 10(-7) M T3) (P < 0.05), and glibenclamide (22% +/- 7% dilation at 10(-7) M T3) (P < 0.01), but it was not affected by propranolol (37% +/- 20% dilation at 10(-7) M T3) (P = 0.99). We conclude that thyroid hormones possess direct vasodilatory effects with both endothelium-independent and endothelium-dependent components.

IMPLICATIONS

Thyroid hormones may have modest direct vasodilatory effects. This may partially account for the cardiovascular actions of the hormones in hyperthyroidism or when administered pharmacologically in cardiac surgery.

摘要

未标注

本研究检验了激素具有直接血管舒张作用这一假说，并试图确定这些作用是否依赖于内皮。解剖出直径约100微米的大鼠骨骼肌阻力动脉，使用视频检测系统监测血管直径变化。在37℃平衡后，用1微摩尔的血栓素类似物U46619预收缩每条血管，在暴露于浓度不断增加的三碘甲状腺原氨酸（T3）或左旋甲状腺素（T4）（10⁻¹⁰至10⁻⁷摩尔）后测量舒张百分比。在内皮剥脱以及用10微摩尔的一氧化氮（NO）合酶抑制剂NG-硝基-L-精氨酸（L-NNA）、10微摩尔的环氧化酶抑制剂吲哚美辛、1微摩尔的三磷酸腺苷敏感性钾通道阻滞剂格列本脲或1微摩尔的β-肾上腺素能拮抗剂普萘洛尔预处理后，也测量对T3的舒张反应。T3和T4均显示出对U46619预收缩血管的浓度依赖性舒张（各P < 0.001），T3的作用大于T4（P < 0.05）（10⁻⁷摩尔T3时舒张36%±9%[平均值±标准差]，10⁻⁷摩尔T4时舒张24%±6%）。相比之下，10⁻⁷摩尔的异丙肾上腺素产生56%±6%的舒张。内皮剥脱（10⁻⁷摩尔T3时舒张18%±3%）（P < 0.01）、L-NNA（10⁻⁷摩尔T3时舒张15%±7%）（P < 0.01）、吲哚美辛（10⁻⁷摩尔T3时舒张20%±9%）（P < 0.05）和格列本脲（10⁻⁷摩尔T3时舒张22%±7%）（P < 0.01）使T3介导的血管舒张减弱但未消除，但它不受普萘洛尔影响（10⁻⁷摩尔T3时舒张37%±20%）（P = 0.99）。我们得出结论，甲状腺激素具有直接血管舒张作用，包括不依赖于内皮和依赖于内皮的成分。