Savage M W, Bodmer C W, Walker A B, Buchan I E, Masson E A, Williams G
Department of Medicine, University of Liverpool, UK.
Eur J Clin Invest. 1995 Dec;25(12):974-9. doi: 10.1111/j.1365-2362.1995.tb01976.x.
The study aimed to assess vascular reactivity to noradrenaline with and without neuropeptide Y in diabetic rats, and to determine whether any abnormality could be attributed to insulin deficiency or to hyperglycaemia per se. The authors compared non-diabetic rats (n = 9) and rats with streptozotocin-induced diabetes that were either untreated (n = 10), or treated with insulin (n = 9) or food restriction (n = 8) to restore near-normoglycaemia. After 4 weeks of diabetes, contractile responses to noradrenaline (0.24-48 mumol L-1), without and with neuropeptide Y (0.1 mumol L-1), were assessed using an isometric myograph in two mesenteric arteries from each rat. Vessels from untreated diabetic rats were significantly more reactive to noradrenaline than the control vessels when tested without (P < 0.0001) but not with (P = NS) neuropeptide Y. Diabetic rats rendered nearly normoglycaemic through food restriction showed dose-response curves that were very similar to the untreated diabetic group (P = NS). By contrast, insulin-treated diabetic vessels showed reduced sensitivity to noradrenaline, with and without neuropeptide Y, compared with both the diet-restricted and untreated vessels (both P < 0.0001). The authors conclude that vascular sensitivity to noradrenaline, without or with neuropeptide Y, is reduced over a wide dose range in vessels taken from rats treated in vivo with insulin; furthermore, vessels taken from diabetic rats not treated with insulin (hypoinsulinaemic) tended to be more reactive than either control vessels or those taken from the insulin-treated rats. The latter group of rats were probably hyperinsulinaemic for much of the time; the results may therefore support the hypothesis that insulin acts as a vasodilator.
该研究旨在评估糖尿病大鼠在有和没有神经肽Y的情况下对去甲肾上腺素的血管反应性，并确定任何异常是否可归因于胰岛素缺乏或高血糖本身。作者比较了非糖尿病大鼠（n = 9）和链脲佐菌素诱导的糖尿病大鼠，后者要么未治疗（n = 10），要么用胰岛素治疗（n = 9）或食物限制（n = 8）以恢复接近正常血糖水平。糖尿病4周后，使用等长肌张力描记器评估每只大鼠两条肠系膜动脉对去甲肾上腺素（0.24 - 48 μmol L-1）在有和没有神经肽Y（0.1 μmol L-1）情况下的收缩反应。在没有神经肽Y（P < 0.0001）但有神经肽Y时（P = 无显著性差异）进行测试时，未治疗的糖尿病大鼠的血管对去甲肾上腺素的反应性明显高于对照血管。通过食物限制使血糖接近正常的糖尿病大鼠显示出与未治疗的糖尿病组非常相似的剂量反应曲线（P = 无显著性差异）。相比之下，与饮食限制组和未治疗组的血管相比，胰岛素治疗的糖尿病血管对去甲肾上腺素的敏感性降低，无论有无神经肽Y（均P < 0.0001）。作者得出结论，在体内用胰岛素治疗的大鼠所取血管中，无论有无神经肽Y，在很宽的剂量范围内对去甲肾上腺素的血管敏感性均降低；此外，未用胰岛素治疗（低胰岛素血症）的糖尿病大鼠所取血管往往比对照血管或胰岛素治疗大鼠所取血管反应性更高。后一组大鼠在大部分时间可能处于高胰岛素血症状态；因此，结果可能支持胰岛素作为血管舒张剂的假说。
