Sapienza P, Edwards J D, Mingoli A, McGregor P E, Cavallari N, Agrawal D K
Department of Surgery, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
J Surg Res. 1996 May;62(2):192-6. doi: 10.1006/jsre.1996.0194.
Ischemia produces functional and structural alterations in peripheral blood vessels. Our study was designed to investigate alpha-adrenoceptor modifications induced by prolonged ischemia and their role in enhancing the contractile response during reperfusion in canine femoral arteries. Unilateral vessel ischemia was created by double crossclamping a femoral artery and was maintained for 3 hr. Reperfusion was allowed for 1 hr. The contralateral femoral artery was utilized as a control. The vessels were harvested for contractile and binding studies. Isometric tension studies revealed that the magnitude of the maximum contractile response to norepinephrine (NE), potassium chloride (KCl), and methoxamine was 671 +/- 82 mg/mm2 versus 245 +/- 43 mg/mm2 (P < 0.01), 485 +/- 46 mg/mm2 versus 229 +/- 62 mg/mm2 (P < 0.05), and 486 +/- 88 mg/mm2 versus 126 +/- 38 mg/mm2 (P < 0.01), respectively for ischemic and nonischemic femoral arteries. EC50 values showed that ischemic vessels were more sensitive to NE, KCl, and methoxamine (P < 0.05). Sodium nitroprusside induced concentration-dependent and complete relaxation in all arterial rings (100% relaxation) but the ischemic femoral artery showed less sensitivity (P < 0.05). Binding studies showed that the number of binding sites (Bmax) for [3H]Prazosin and [3H]Rauwolscine were significantly increased in ischemic versus nonischemic vessels (1261 +/- 95 fmole/mg versus 704 +/- 113 fmole/mg, P < 0.03, and 490 +/- 86 fmole/mg versus 175 +/- 15 fmole/mg, P < 0.04, respectively). Furthermore, a significant decrease in affinity (Kd) for [3H]Prazosin and [3H]Rauwolscine was observed in ischemic versus nonischemic tissues (9.4 +/- 1.7 nM versus 4 +/- 0.2 nM, P < 0.02, and 6.4 +/- 1.5 nM versus 1.8 +/- 0.6 nM, P < 0.01, respectively). The increase in canine femoral artery vasoreactivity, following prolonged ischemia, seems to be also due to an increased density and functional activity of alpha-adrenoceptors expressed by the ischemic arterial smooth muscle cells.
缺血会在外周血管中产生功能和结构上的改变。我们的研究旨在探究长时间缺血诱导的α-肾上腺素能受体修饰及其在犬股动脉再灌注期间增强收缩反应中的作用。通过双重交叉夹闭股动脉造成单侧血管缺血，并维持3小时。给予1小时的再灌注时间。对侧股动脉用作对照。采集血管用于收缩和结合研究。等长张力研究显示，缺血性和非缺血性股动脉对去甲肾上腺素（NE）、氯化钾（KCl）和甲氧明的最大收缩反应幅度分别为671±82mg/mm2 对245±43mg/mm2（P<0.01）、485±46mg/mm2对229±62mg/mm2（P<0.05）和486±88mg/mm2对126±38mg/mm2（P<0.01）。半数有效浓度（EC50）值表明，缺血血管对NE、KCl和甲氧明更敏感（P<0.05）。硝普钠在所有动脉环中诱导浓度依赖性和完全舒张（100%舒张），但缺血性股动脉的敏感性较低（P<0.05）。结合研究表明，与非缺血性血管相比，缺血性血管中[3H]哌唑嗪和[3H]萝芙木碱的结合位点数量（Bmax）显著增加（分别为1261±95fmol/mg对704±113fmol/mg，P<0.03；490±86fmol/mg对175±15fmol/mg，P<0.04）。此外，与非缺血性组织相比，缺血性组织中对[3H]哌唑嗪和[3H]萝芙木碱的亲和力（Kd）显著降低（分别为9.4±1.7nM对4±0.2nM，P<0.02；6.4±1.5nM对1.8±0.6nM，P<0.01）。长时间缺血后犬股动脉血管反应性的增加似乎也归因于缺血性动脉平滑肌细胞表达的α-肾上腺素能受体密度和功能活性的增加。
