Legan E
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock 79430.
Life Sci. 1989;45(5):371-8. doi: 10.1016/0024-3205(89)90622-x.
Altered vascular sensitivity and responsiveness has been previously described in various stages of experimental diabetes mellitus. Increases in membrane bound Ca2+ and intracellular calcium in diabetic aorta have been postulated to explain excitation-coupling dysfunction in diabetic vascular smooth muscle (VSM). Receptor-mediated phosphatidylinositol (PI) hydrolysis is known to activate VSM contraction; thus contractile changes in diabetic aorta could be functionally linked to abnormal PI turnover. To evaluate this possibility, parallel experiments were undertaken to study contractility and receptor-stimulated PI turnover with norepinephrine (NE), phenylephrine (PE), and serotonin (5-HT). At 7 and 28 days following injection of streptozotocin with production of the hyperglycemic state, aortas were harvested for contractile and PI turnover experiments. No differences in the contractile cumulative dose responses or receptor-mediated PI turnover were measured in the 7 day group. At 28 days, vascular supersensitivity and increased responsiveness were observed. PI hydrolysis in basal and agonist-stimulated aorta was, however, markedly decreased at 28 days. These findings suggest that mobilization and utilization of Ca2+ during contraction occur independently of receptor-stimulated PI hydrolysis in aorta from hyperglycemic rats. The duration of hyperglycemia also significantly effects contractility and PI turnover in rat aorta.
血管敏感性和反应性的改变先前已在实验性糖尿病的各个阶段有所描述。糖尿病主动脉中膜结合钙和细胞内钙的增加被认为可以解释糖尿病血管平滑肌（VSM）中的兴奋-偶联功能障碍。已知受体介导的磷脂酰肌醇（PI）水解可激活VSM收缩；因此，糖尿病主动脉中的收缩变化可能在功能上与异常的PI代谢相关。为了评估这种可能性，我们进行了平行实验，以研究去甲肾上腺素（NE）、苯肾上腺素（PE）和5-羟色胺（5-HT）对收缩性和受体刺激的PI代谢的影响。在注射链脲佐菌素导致高血糖状态后的第7天和第28天，采集主动脉进行收缩性和PI代谢实验。在第7天的组中，未检测到收缩累积剂量反应或受体介导的PI代谢有差异。在第28天，观察到血管超敏反应和反应性增加。然而，在第28天，基础和激动剂刺激的主动脉中的PI水解明显减少。这些发现表明，高血糖大鼠主动脉收缩过程中Ca2+的动员和利用独立于受体刺激的PI水解。高血糖的持续时间也显著影响大鼠主动脉的收缩性和PI代谢。
