Endogenous sulfur dioxide(SO_(2) )is a novel gasotransmitter involved in the pathophysiologic process of pulmonary artery hypertension(PAH).However,the molecular pathways on which endogenous SO_(2) impact remains uncl...Endogenous sulfur dioxide(SO_(2) )is a novel gasotransmitter involved in the pathophysiologic process of pulmonary artery hypertension(PAH).However,the molecular pathways on which endogenous SO_(2) impact remains unclarified.Methods In the present study,the regulatory role of endogenous SO_(2) in the pathogenesis of PAH and its associated molecular mechanisms were investigated.A Wistar rat model of PAH induced by hypoxic exposure was established.Endogenous SO_(2) content in rat plasma and rat lungs,mean PAH,ratio of right ventricular/(left ventricular+septum)[RV/(LV+SP)]and body weight of Wistar rats were examined.Protein expression of aspartate aminotransferase 1(AAT1),endothelial nitric oxide synthase(e NOS)and Rho-associated coiled kinase(ROCK)in rat lung tissues were determined by western blot.Activation of AAT1 and Ras homolog gene family member A(Rho A)in rat lungs were detected by assay kits according to manufacturers’instructions.The concentration of nitric oxide(NO),level of cyclic guanosine monophosphate(c GMP)and activity of protein kinase G(PKG)in rat lung tissues after exposure to hypoxic conditions or treatment with SO_(2) donor were also examined using commercial kits.Results Our data showed that the endogenous SO_(2) /AAT1 pathway was markedly downregulated in rats with PAH induced by hypoxic exposure.However,SO_(2) donor upregulated the endogenous SO_(2) pathway and attenuated PAH.Further investigation revealed that in the PAH model,the e NOS/c GMP/PKG cascade was downregulated and the Rho A/ROCK pathway was upregulated,which could be reversed by SO_(2) donor.Conclusions In conclusion,the endogenous SO_(2) /AAT1 pathway might protect against the development of hypoxic exposure induced PAH by promoting the e NOS/c GMP/PKG cascade and downregulating Rho A/ROCK pathway.展开更多
基金supported by National Natural Science Founds of China(No.81900285)Science and Technology Program of Guangzhou,China(No.202002030317)Guangdong Basic and Applied Basic Research Foundation(No.2020A1515010242)。
文摘Endogenous sulfur dioxide(SO_(2) )is a novel gasotransmitter involved in the pathophysiologic process of pulmonary artery hypertension(PAH).However,the molecular pathways on which endogenous SO_(2) impact remains unclarified.Methods In the present study,the regulatory role of endogenous SO_(2) in the pathogenesis of PAH and its associated molecular mechanisms were investigated.A Wistar rat model of PAH induced by hypoxic exposure was established.Endogenous SO_(2) content in rat plasma and rat lungs,mean PAH,ratio of right ventricular/(left ventricular+septum)[RV/(LV+SP)]and body weight of Wistar rats were examined.Protein expression of aspartate aminotransferase 1(AAT1),endothelial nitric oxide synthase(e NOS)and Rho-associated coiled kinase(ROCK)in rat lung tissues were determined by western blot.Activation of AAT1 and Ras homolog gene family member A(Rho A)in rat lungs were detected by assay kits according to manufacturers’instructions.The concentration of nitric oxide(NO),level of cyclic guanosine monophosphate(c GMP)and activity of protein kinase G(PKG)in rat lung tissues after exposure to hypoxic conditions or treatment with SO_(2) donor were also examined using commercial kits.Results Our data showed that the endogenous SO_(2) /AAT1 pathway was markedly downregulated in rats with PAH induced by hypoxic exposure.However,SO_(2) donor upregulated the endogenous SO_(2) pathway and attenuated PAH.Further investigation revealed that in the PAH model,the e NOS/c GMP/PKG cascade was downregulated and the Rho A/ROCK pathway was upregulated,which could be reversed by SO_(2) donor.Conclusions In conclusion,the endogenous SO_(2) /AAT1 pathway might protect against the development of hypoxic exposure induced PAH by promoting the e NOS/c GMP/PKG cascade and downregulating Rho A/ROCK pathway.
