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