Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

Wang, Chen; Du, Hui-Bo; Zhao, Zhen-Ao; Zhai, Jia-Yi; Zhang, Limin; Niu, Chun‐Yu; Zhao, Zi‐Gang

doi:10.3389/fphys.2021.728191

Cited by 3 publications

(7 citation statements)

References 42 publications

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“…The aim of part 3 was to confirm the suppressive role of SGB in PHSML-mediated phenotypic transformation through autophagy inhibition in rat VSMCs. Briefly, VSMCs were treated with various lymph types for 48 h as follows: control, PHSML (4%), PHSML-SGB (4%), PHSML plus 3-MA (5 mM [9]), and PHSML-SGB plus RAPA (30 nM [23]).…”

Section: Methodsmentioning

confidence: 99%

“…Next, 5 μL of fluorescein-labeled BSA at a concentration of 4 mg/mL and 100 μL of norepinephrine (NE) solution at a concentration of 5 nM were sequentially added to the apical chamber. Cellular contractility was evaluated based on the permeability of fluorescein-labeled BSA, which was calculated according to the fluorescein accumulative filtration rate to fluorescein-labeled BSA, as previously described (9).…”

Section: Contractile Response Of Vsmcsmentioning

confidence: 99%

“…Vascular hyporeactivity exerts an important adverse effect during hemorrhagic shock, leading to circulatory failure and refractory shock (6–8). The previous investigations have showed that the mechanism by which PHSML induces vascular hyporeactivity is related to the calcium desensitization (4) and excessive autophagy of vascular smooth muscle cells (VSMCs) (9). However, the detailed mechanism by which PHSML induces autophagy in VSMCs requires further investigation.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, therapies targeting nervous system regulation may be a new approach for hemorrhagic shock treatment. Previous studies have shown that stellate ganglion block (SGB) pre-or post-treatment prolongs survival time and reduces hemorrhagic shock-induced intestinal barrier injury and acute lung injury (12,13), and SGB inhibits PHSML-mediated vascular hyporeactivity by reducing excessive autophagy in VSMCs (9). Based on the experimental findings that autophagy induces phenotypic transformation of VSMCs and decreases systolic protein-induced calcium desensitization in VSMCs involved in hemorrhagic shock-induced vascular hyporeactivity (14), we hypothesized that the role of SGB in reversing PHSML-mediated vascular hyporeactivity is associated with the inhibition of autophagy-mediated phenotypic transformation.…”

Section: Introductionmentioning

confidence: 99%

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STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

Li,

Du,

Zhao

et al. 2023

Shock

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Post-hemorrhagic shock mesenteric lymph (PHSML) return-contributed excessive autophagy of vascular smooth muscle cells (VSMCs) is involved in vascular hypo-reactivity, which is inhibited by stellate ganglion block (SGB) treatment. The contractile phenotype of VSMCs transforms into a synthetic phenotype after stimulation with excessive autophagy. Therefore, we hypothesized that SGB ameliorates PHSML-induced vascular hypo-reactivity by inhibiting autophagy-mediated phenotypic transformation of VSMCs. To substantiate this hypothesis, a hemorrhagic shock model in conscious rats was employed to observe the effects of SGB intervention or intravenous infusion of the autophagy inhibitor 3-MA on intestinal blood flow and the expression of autophagy- and phenotype-defining proteins in mesenteric secondary artery tissues. We also investigated the effects of intraperitoneal administration of PHSML intravenous infusion and the autophagy agonist rapamycin (RAPA) on the beneficial effect of SGB. The results showed that hemorrhagic shock decreased intestinal blood flow and enhanced the expression of LC3 II/I, Beclin1, and matrix metalloproteinase 2, which were reversed by SGB or 3-MA treatment. In contrast, RAPA and PHSML administration abolished the beneficial effects of SGB. Furthermore, the effects of PHSML or PHSML obtained from rats treated with SGB (PHSML-SGB) on cellular contractility, autophagy, and VSMC phenotype were explored. Meanwhile, the effects of 3-MA on PHSML and RAPA on PHSML-SGB were observed. The results showed that PHSML, but not PHSML-SGB, incubation decreased VSMCs contractility and induced autophagy activation and phenotype transformation. Importantly, 3-MA administration reversed the adverse effects of PHSML, and RAPA treatment attenuated the effects of PHSML-SGB incubation on VSMCs. Taken together, the protective effect of SGB on vascular reactivity is achieved by inhibiting excessive autophagy-mediated phenotypic transformation of VSMCs to maintain their contractile phenotype.

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Section: Methodsmentioning

confidence: 99%

Section: Contractile Response Of Vsmcsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

Li,

Du,

Zhao

et al. 2023

Shock

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“…The surgery was carried out under inhalation anesthesia in all rats as previous described (20,21). After surgical procedures, the inhalation anesthesia was removed.…”

Section: Acute Hemorrhage and Various Treatments In Conscious Ratsmentioning

confidence: 99%

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Sun

Zhang

et al. 2023

Shock

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Background: Hemorrhagic shock–induced acute lung injury (ALI) is commonly associated with the posthemorrhagic shock mesenteric lymph (PHSML) return. Whether excessive autophagy is involved in PHSML-mediated ALI remains unclear. The relationship between estrogen treatment and PHSML or autophagy needs to verify. The current study will clarify the role of estrogen in reducing PHSML-mediated ALI through inhibition of autophagy. Methods: First, a hemorrhagic shock model in conscious rats was used to observe the effects of 17β-estradiol (E2) on intestinal blood flow, pulmonary function, intestinal and pulmonary morphology, and expression of autophagy marker proteins. Meanwhile, the effect of PHSML and autophagy agonist during E2 treatment was also investigated. Secondly, rat primary pulmonary microvascular endothelial cells were used to observe the effect of PHSML, PHSML plus E2, and E2-PHSML (PHSML obtained from rats treated by E2) on the cell viability. Results: Hemorrhagic shock induced intestinal and pulmonary tissue damage and increased wet/dry ratio, reduced intestinal blood flow, along with pulmonary dysfunction characterized by increased functional residual capacity and lung resistance and decreased inspiratory capacity and peak expiratory flow. Hemorrhagic shock also enhanced the autophagy levels in intestinal and pulmonary tissue, which was characterized by increased expressions of LC3 II/I and Beclin-1 and decreased expression of p62. E2 treatment significantly attenuated these adverse changes after hemorrhagic shock, which was reversed by PHSML or rapamycin administration. Importantly, PHSML incubation decreased the viability of pulmonary microvascular endothelial cells, while E2 coincubation or E2-treated lymph counteracted the adverse roles of PHSML. Conclusions: The role of estrogen reducing PHSML-mediated ALI is associated with the inhibition of autophagy.

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Estrogen activates its receptors to improve lymphatic contractility through suppression of endoplasmic reticulum stress induced by hemorrhagic shock

Zhao

2023

Preprint

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Lymphatic contractility dysfunction is associated with the deterioration of hemorrhagic shock (HS). Endoplasmic reticulum stress (ERS) has been demonstrated to be involved in HS-induced organ injury, while estrogen alleviates HS-induced ERS and organ injury. However, whether estrogen improves lymphatic contraction through inhibition of HS-induced ERS remains unclear. We hypothesized that estrogen activation of its receptors (ERs) promoted mesenteric lymphatic contractility through suppression of HS-induced ERS in lymphatic smooth muscle cells (LSMCs). In a rodent model of HS, 17β-estradiol (E2) administration abrogated HS-induced upregulation of GRP78 in lymphatic tissues. Either E2 or ERS inhibitor 4-phenylbutyric acid (4-PBA) promoted the survival HS rats in the first 72 hours after resuscitation. E2, ER-α agonist PPT, ER-β agonist DPN, GPR30-selective agonist G-1, 4-PBA significantly enhanced the contractility of mesenteric lymphatics following HS in vivo and in vitro. In contrast, ICI 182,780 (ERα and ERβ selective inhibitor) and G-15 (GPR30-selective inhibitor) partly abolished the beneficial effects of E2. Furthermore, ERS agonist XCT-790 abolished the beneficial effects of E2, PPT, DPN, and G-1 on lymphatic contractility. Additionally, E2, PPT, DPN, and G-1 inhibited ERS, and thus ameliorate ERS agonist tunicamycin-induced hypo-contractility in primary LSMCs. Taken together, the data indicates that E2 promotes the lymphatic contractility after HS by inhibiting ERS and estrogen receptor activation mediates the beneficial effect of E2.

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Autophagy Is Involved in Stellate Ganglion Block Reversing Posthemorrhagic Shock Mesenteric Lymph-Mediated Vascular Hyporeactivity

Cited by 3 publications

References 42 publications

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

STELLATE GANGLION BLOCK REVERSES PHSML-INDUCED VASCULAR HYPOREACTIVITY THROUGH INHIBITING AUTOPHAGY-MEDIATED PHENOTYPIC TRANSFORMATION OF VSMCs

Estrogen Alleviates Posthemorrhagic Shock Mesenteric Lymph-Mediated Lung Injury Through Autophagy Inhibition

Estrogen activates its receptors to improve lymphatic contractility through suppression of endoplasmic reticulum stress induced by hemorrhagic shock

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