Glucose-6 phosphate dehydrogenase deficiency decreases the vascular response to angiotensin II
Glucose-6 phosphate dehydrogenase deficiency decreases the vascular response to angiotensin II
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DOI：
10.1161/circulationaha.104.499095
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发表时间：
2005-07-12
期刊：
影响因子：
37.8
通讯作者：
Cohen, RA
中科院分区：
文献类型：
--
作者：
Matsui, R;Xu, SQ;Cohen, RA
背景-葡萄糖-6-磷酸脱氢酶（G6 PD）通过戊糖磷酸途径调节还原型NADPH的产生。因此，G6 PD可能通过血管NADPH氧化酶影响超氧阴离子的产生，这是介导血管对血管紧张素II（Ang II）反应的关键。我们确定了高血压和血管肥大反应，以血管紧张素Ⅱ在G6 PD缺陷mice.Methods和Results -血管紧张素Ⅱ（0.7毫克/公斤，每天）通过皮下渗透泵输注6天的雄性半合子G6 PD突变体（G6 PD（mat））和野生型（WT）C3 H小鼠。（1）与野生型相比，G6 PD（mut）小鼠主动脉G6 PD活性降低10%~ 20%，NADPH活性降低50%。（2）G6 PDmut小鼠的基础收缩压无显著差异（WT 88 +/- 4 mmHg vs G6 PD（mut）95 +/- 4 mmHg），但Ang II使G6 PDmut小鼠的血压升高至较低水平（WT 139 +/- 4 mmHg vs G6 PDmut 123 +/- 5 mmHg; P < 0.05）。(3)Ang II增加G6 PDmut小鼠主动脉中膜厚度较少（WT 71 +/- 2 μ m vs G6 PD（mut）62 +/- 1 μ m; P < 0.01）。(4)在G6 PDmut小鼠中，Ang II较少增加主动脉中的3-o-硝基酪氨酸染色和二氢乙锭氧化。（5）从G6 PDmut小鼠分离的平滑肌细胞显示出较少的Ang II诱导的Akt和p42/44 ERK磷酸化。结论-G6 PD缺陷可能通过限制NADPH氧化酶底物的产生来减少血管超氧阴离子的产生，从而抑制氧化剂介导的Ang II诱导的信号通路，该通路有助于高血压和平滑肌肥大。
Background - Glucose-6-phosphate dehydrogenase (G6PD) regulates production of the reduced form of NADPH through the pentose phosphate pathway. G6PD may therefore affect superoxide anion production via vascular NADPH oxidase, which is key in mediating the vascular response to angiotensin II (Ang II). We determined the hypertensive and vascular hypertrophic response to Ang II in G6PD-deficient mice.Methods and Results - Ang II (0.7 mg/kg per day) was infused via subcutaneous osmotic pumps for 6 days in male hemizygote G6PD mutant (G6PD(mat)) and wild-type (WT) C3H mice. ( 1) Compared with WT, G6PD(mut) mouse aorta had 10% to 20% of G6PD activity and 50% less NADPH. ( 2) Basal systolic blood pressure was not significantly different in G6PDmut mice (WT 88 +/- 4 mm Hg versus G6PD(mut) 95 +/- 4 mm Hg), but Ang II increased blood pressure to a lower level in G6PDmut mice (WT 139 +/- 4 mm Hg versus G6PDmut 123 +/- 5 mm Hg; P < 0.05). (3) Ang II increased aortic medial thickness less in G6PDmut mice (WT 71 +/- 2 mu m versus G6PD(mut) 62 +/- 1 mu m; P < 0.01). (4) 3-o-Nitrotyrosine staining and dihydroethidium oxidation in the aorta was increased by Ang II less in G6PDmut mice. ( 5) Smooth muscle cells isolated from G6PDmut mice showed less Ang II - induced phosphorylation of Akt and p42/44 ERK.Conclusions - G6PD deficiency may reduce vascular superoxide anion production by limiting production of the substrate for NADPH oxidase, thereby inhibiting oxidant-mediated Ang II - induced signaling pathways that contribute to hypertension and smooth muscle hypertrophy.