Pape D, Beuchard J, Guillo P, Allain H, Bellissant E
Laboratoire de Pharmacologie Expérimentale et Clinique, Faculté de Médecine, Rennes, France.
Fundam Clin Pharmacol. 1997;11(2):121-6. doi: 10.1111/j.1472-8206.1997.tb00178.x.
The effects of hypoxia on isolated arteries remain controversial, depending on the species, vascular beds and protocols. The aims of the study were to characterize the response of rat thoracic aorta to hypoxia and to examine the roles of endothelium, extracellular calcium and endothelin in this response. Hypoxia was induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2. Experiments were performed during 1 h in norepinephrine (0.01 microM) precontracted rings. Hypoxia produced a biphasic response consisting of an initial transient partial relaxation (67% at 14 min) followed by a slow but sustained contraction (27% from 40 to 60 min). After endothelium removal, relaxation appeared faster with increased magnitude (82% at 12 min) and was followed by a weak transient contraction (16% at 25 min). In endothelium-intact rings, Ca2+ free medium (EGTA, 0.1 mM) and Ca2+ channel blockers, verapamil (0.05, 0.5 and 5 microM) or nicardipine (0.1, 1 and 10 microM), had no effect on relaxation but inhibited the contraction, the effects of both calcium antagonists being concentration-dependent. Similarly, the ETA/ETB receptor antagonist, bosentan (0.1, 10 and 1,000 nM), induced a concentration-dependent decrease in the contraction. We conclude that 1) the response of rat thoracic aorta during 1 h of hypoxia is biphasic (relaxation followed by contraction); 2) the endothelium is involved in the contraction whereas its role in the relaxation remains to be elucidated; 3) extracellular calcium is involved in the contraction; and 4) endothelin may play a role in the contraction.
缺氧对离体动脉的影响仍存在争议，这取决于物种、血管床和实验方案。本研究的目的是描述大鼠胸主动脉对缺氧的反应，并研究内皮、细胞外钙和内皮素在该反应中的作用。通过用95% N₂和5% CO₂代替95% O₂和5% CO₂鼓泡Krebs溶液来诱导缺氧。实验在去甲肾上腺素（0.01微摩尔）预收缩的血管环中进行1小时。缺氧产生双相反应，包括最初短暂的部分舒张（14分钟时为67%），随后是缓慢但持续的收缩（40至60分钟时为27%）。去除内皮后，舒张出现得更快且幅度增加（12分钟时为82%），随后是微弱的短暂收缩（25分钟时为16%）。在内皮完整的血管环中，无钙培养基（EGTA，0.1毫摩尔）和钙通道阻滞剂维拉帕米（0.05、0.5和5微摩尔）或尼卡地平（0.1、1和10微摩尔）对舒张无影响，但抑制收缩，两种钙拮抗剂的作用均呈浓度依赖性。同样，ETA/ETB受体拮抗剂波生坦（0.1、10和1000纳摩尔）诱导收缩呈浓度依赖性降低。我们得出结论：1）大鼠胸主动脉在1小时缺氧期间的反应是双相的（舒张后收缩）；2）内皮参与收缩，但其在舒张中的作用尚待阐明；3）细胞外钙参与收缩；4）内皮素可能在收缩中起作用。
