Changes in arterial hydrogen sulfide (H2S) content during septic shock and endotoxin shock in rats

doi:10.1016/S0163-4453(03)00043-4

Journal of Infection

Volume 47, Issue 2, August 2003, Pages 155-160

https://doi.org/10.1016/S0163-4453(03)00043-4 Get rights and content

Abstract

Objectives: To explore the changes of hydrogen sulfide (H₂S) in vascular tissues of rats with septic shock and endotoxin shock and its possible pathophysiological implication. Methods: Rat models of septic shock induced by cecal ligation and puncture and of endotoxic shock induced by injection of endotoxin were used in this study. The authors measured hymodynamic variations, metabolic data, H₂S and nitric oxide (NO) contents of different arteries in rats with septic shock and endotoxic shock. Results: The results showed that hemodynamic parameters including the heart rate (HR), the mean arterial pressure (BP), and the +dP/dt max decreased markedly, while the left ventricular end-diastolic pressure (LVEDP) increased significantly and the rats developed hypoglycemia and lactic acidosis. Arterial H₂S contents were significantly increased (P<0.01) in both septic and endotoxic shock (P<0.01). Endogenous H₂S and NO contents all negatively correlated with BP, cardiac function and the degree of hypoglycemia (P<0.01). Conclusions: The results of our study demonstrated that endogenous vascular H₂S increased in rats with septic shock and endotoxic shock. It was suggested that endogenous H₂S was involved in physiological and pathophysiological process during shock.

Introduction

Septic shock is defined as a systemic response to infection. Its major symptoms include a severe fall in blood pressure (hypotension) with hyporeactivity to vasoconstrictor agents (vasoplegia) which may lead to the dysfunction of failure of major organs including lungs, liver, kidneys and brain (multiple organ dysfunction, MODS) and ultimately death. It has been known that the most common cause of septic shock is the invasion of gram-negative bacteria, but the mechanism is unclear yet. In recent years, some small molecular gases such as nitric oxide (NO) and carbon monoxide (CO) are considered to be very important in the pathogenesis of many diseases along with the progress of molecular biology.1., 2., 3. Michael et al. found that NO level was increased in septic shock and both NO and CO were found to play an important role in the regulation of blood pressure and vasorelaxation. However, the pathogenesis of septic shock was not fully understood.⁴ Seeking for noval gaseous molecules which probably play an important part in shock is a new trend of study. Are there any other gaseous messengers interfered with the mechanism and pathogenesis of septic shock as NO and CO or even more important than them?

Hydrogen sulfide (H₂S), which is metabolized from cysteine by pyridoxal-5′-phosphate-dependent enzymes including cystathionine β-synthase (CBS) and /or cystathionine γ-lyase (CSE),5., 6. had been proved to be a neuromodulator in the brain⁷ as well as a tone regulator in smooth muscle⁸ in the middle of 1990’s. We further confirmed that H₂S could suppress the proliferation of smooth muscular cells stimulated with endothelin through down-regulation of activities of mitogen activated protein kinases based on the cultured smooth muscle cells of rats in vitro. However, the physiological effect of endogenous H₂S on vessels in vivo has not been reported yet. How does H₂S change in septic shock and do it act similarly to NO? All these questions inspired our great interests in the following studies. The purpose of the present study was to explore the contents of H₂S in septic shock and endotoxin shock models of rat and to further study the possible role of H₂S in the pathogenesis of septic shock.

Section snippets

Materials

Male Sprague–Dawley (SD) rats, weighing 240–260 g, were purchased from the Animal Center of Peking University Health Science Center. Endotoxin was supplied by DIFCO Lab (America). Aspergillus nitrate reductase, glucose oxidase and lactate kit were all bought from Sigma. Other reagents were of analytical purity. H₂S was produced from the reaction of Na₂S and HCl immediately before use.

Preparation of rat shock models

Sixty-four male rats were randomly divided into four groups: (1) endotoxin shock group (n=20) (2) septic shock

Mortality of the rats

Seven rats in endotoxin shock group and eight rats in septic shock group died while there was no rat died in the control groups. The mortality of rats in endotoxin shock group and septic shock group was 35 and 40%, respectively.

Hemodynamic changes in rats

The heart rate (HR), mean arterial pressure (BP), and +dP/dt max markedly reduced in both septic shock group and endotoxin shock group compared to the controls, while the left ventricular end-diastolic pressure (LVEDP) increased at the same time (Table I).

Changes in the levels of plasma lactate and glucose

Levels of

Discussion

Endogenous H₂S is formed from cysteine by pyridoxal-5′-phosphate-dependent enzymes, including cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). The H₂S-producing enzyme cystathionine β-synthetade is highly expressed in the hippocampus and cerebellum, and it has been determined that brain homogenates produce H₂S.⁷ Physiological concentrations of H₂S facilitated the induction of LTP in the hippocampus, suggesting that endogenous H₂S functioned as a neuromodulator in the brain. In

Acknowledgements

This work was supported by China Major Research Development Project (G2000056905) and Peking University Major Cardiovascular Research Program, a special fund for promotion of education, Ministry of Education, PRC (985 Project).

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Journal of Infection

Abstract

Introduction

Section snippets

Materials

Preparation of rat shock models

Mortality of the rats

Hemodynamic changes in rats

Changes in the levels of plasma lactate and glucose

Discussion

Acknowledgements

References (14)

The possible role of hydrogen sulfide as and endogenous smooth muscle relaxant in synergy with nitric oxide

Biochem Biophys Res Commun

Nitric oxide accounts for the biological activity of endothelium-derived factor

Nature

Biological actions and properties of endothelium-derived nitric oxide formed and released from artery and vein

Circ Res

Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor

Can J Physiol Pharmacol

Nitric oxide in septic shock

Biochim Biophys Acta

Characterization of the enzymic capacity for cysteine desulphhydration in liver and kidney of the rat

Biochem J

Sequence of cDNA for rat cystathionine γ-lyase and comparison of deduced amino acid sequence with related Escherichia coli enzymes

Biochem J

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Sulfur dioxide attenuates hypoxia-induced pulmonary arteriolar remodeling via Dkk1/Wnt signaling pathway