Compensatory role of endogenous sulfur dioxide in nitric oxide deficiency-induced hypertension.-猫眼课题宝

内源性二氧化硫在一氧化氮缺乏所致高血压中的代偿作用

DOI：

10.1016/j.redox.2021.102192

发表时间：

2021-11-18

期刊：

Redox biology

影响因子：

11.4

通讯作者：

中科院分区：

生物学1区

文献类型：

作者：

Song Y;Song J;Zhu Z;Peng H;Ding X;Yang F;Li K;Yu X;Yang G;Tao Y;Bu D;Tang C;Huang Y;Du J;Jin H

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626683/

This study aimed to determine the communicational pattern of gaseous signaling molecules sulfur dioxide (SO2) and nitric oxide (NO) between vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), and elucidate the compensatory role and significance of endogenous SO2 in the development of hypertension due to NO deficiency. Blood pressure was monitored by the tail-cuff and implantable physiological signal telemetry in L-nitro-arginine methyl ester (l-NAME)-induced hypertensive mice, and structural alterations of mouse aortic vessels were detected by the elastic fiber staining method. l-NAME-treated mice showed decreased plasma NO levels, increased SO2 levels, vascular remodeling, and increased blood pressure, and application of l-aspartate-β-hydroxamate, which inhibits SO2 production, further aggravated vascular structural remodeling and increased blood pressure. Moreover, in a co-culture system of HAECs and HASMCs, NO from HAECs did not influence aspartate aminotransferase (AAT)1 protein expression but decreased AAT1 activity in HASMCs, thereby resulting in the inhibition of endogenous SO2 production. Furthermore, NO promoted S-nitrosylation of AAT1 protein in HASMCs and purified AAT1 protein. Liquid chromatography with tandem mass spectrometry showed that the Cys192 site of AAT1 purified protein was modified by S-nitrosylation. In contrast, dithiothreitol or C192S mutations in HASMCs blocked NO-induced AAT1 S-nitrosylation and restored AAT1 enzyme activity. Endothelium-derived NO inhibits AAT activity by nitrosylating AAT1 at the Cys192 site and reduces SO2 production in HASMCs. Our findings suggest that SO2 acts as a compensatory defense system to antagonize vascular structural remodeling and hypertension when the endogenous NO pathway is disturbed. Endogenous NO/SO2 is involved in the control of cardiovascular homeostasis. Disturbed NO generation is compensated by SO2 to protect against hypertension. Endothelium-derived NO inhibits AAT activity by nitrosylating AAT1 at Cys192. NO-inhibited SO2 generation might be a mechanism underlying cellular communication.