Williams B, Schrier R W
Department of Medicine, University of Colorado School of Medicine, Denver.
Miner Electrolyte Metab. 1992;18(2-5):145-50.
Blood flow autoregulation is impaired in early diabetes mellitus, predisposing the microvasculature to injury. Blood flow autoregulation is in part a myogenic response that is critically dependent on Ca2+ uptake via voltage-sensitive calcium channels in vascular smooth muscle cells (VSMC). Recent evidence suggests that impairment of blood flow autoregulation in diabetes may be responsive to variations in glycemic control. The present study thus examined the independent effect of an elevated extracellular glucose concentration on Ca2+ uptake by cultured rat VSMC in vitro. A threshold glucose concentration of 15-20 mmol/l markedly and maximally depressed basal and voltage sensitive Ca2+ channel activated (BAY K 8644, 10(-7) M) Ca2+ uptake. This effect was apparent within 3 h of incubating VSMC with the high glucose medium and was maximal after 48 h incubation. Osmotic control media containing either mannitol or L-glucose did not inhibit Ca2+ uptake by VSMC, thus confirming the effect was specific for elevated extracellular glucose concentrations and unrelated to changes in extracellular osmolality. Glucose-induced inhibition of basal and voltage-sensitive transmembrane fluxes of Ca2+ in VSMC may provide a metabolic mechanism for impaired calcium-dependent blood flow autoregulatory responses in early diabetes mellitus.
在糖尿病早期，血流自动调节功能受损，使微血管易受损伤。血流自动调节部分是一种肌源性反应，它严重依赖于血管平滑肌细胞（VSMC）通过电压敏感性钙通道摄取Ca2+。最近的证据表明，糖尿病患者血流自动调节功能的损害可能与血糖控制的变化有关。因此，本研究在体外检测了细胞外葡萄糖浓度升高对培养的大鼠VSMC摄取Ca2+的独立影响。15 - 20 mmol/l的阈值葡萄糖浓度显著且最大程度地降低了基础和电压敏感性Ca2+通道激活（BAY K 8644，10(-7) M）时的Ca2+摄取。在用高糖培养基孵育VSMC的3小时内，这种效应就很明显，孵育48小时后达到最大。含有甘露醇或L - 葡萄糖的渗透压对照培养基并未抑制VSMC摄取Ca2+，从而证实该效应是细胞外葡萄糖浓度升高所特有的，与细胞外渗透压的变化无关。葡萄糖诱导的VSMC中基础和电压敏感性Ca2+跨膜通量的抑制可能为糖尿病早期钙依赖性血流自动调节反应受损提供一种代谢机制。
