Hydrogen Sulfide In The Paraventricular Nucleus Contribute To Chronic Intermittent Hypoxia Induced-hypertension In Rats

BackgroundHypertension is a common and serious cardiovascular diseases to human health,and in the clinical，hypertension has a very close relationship between obstructive sleepapnea syndrome (OSAS). Sleep apnea can produce chronic intermittent hypoxia, whichis considered to be the most important factor in causing hypertension. Hypothalamicparaventricular nucleus (PVN) is an important nuclear group to integrate thecardiovascular events, which can control the sympathetic preganglionic neurons andcardiovascular events, and also closely associated with the incidence and maintenanceof hypertension. Hydrogen sulfide (H2S) is now recognized as an important signalingmolecule and has been shown to have so dilator and cardio-protectant effects. Therefore,we speculate that the H2S in PVN is likely the important signaling molecules involvedin the CIH induced-hypertension in ratsObjective1To research that the role of H2S in PVN in chronic intermittent hypoxia-inducedhypertension and its mechanism.2To observe the therapeutic effect of chronic intermittent hypoxia-inducedhypertension by elevating the level of H2S. MethodsUsing Powerlab tail artery pressure measurement system monitored systolic bloodpressure (SBP) after establishing the model of hypertension caused by chronicintermittent hypoxia. The bilateral PVN microinjections were performed withstereotaxic instrument, and renal sympathetic nerve activity (RSNA), mean arterialpressure (MAP), heart rate (HR) were recorded in vivo on a PowerLab data acquisitionsystem. The activity of cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE)was detected by enzyme-linked immunoassay (ELISA) kits.1Establishing the model of hypertension caused by chronic intermittent hypoxiaThe rats were randomly divided into control group (Control) and chronic intermittenthypoxia group (CIH). Control group rats were deal with same process as CIH groupexcept for executing chronic intermittent hypoxia. Rats of CIH group treated withchronic intermittent hypoxia for15days.All of the rats were use the tail cuff detectedSBP and the Powerlab biological signal acquisition system observed the MAP, RSNA,HR of rats.2Effects of chronic intermittent hypoxia on the level of H2S, the activity of CBSand CSEThe level of H2S content were detected by GENMED organization colorimetricquantification assay kit to observe whether chronic intermittent hypoxia reduced thelevels of H2S in rats Using ELISA kits to detect the changes of CBS and CSE activity inPVN of Control group and CIH rats. 3The influence of acutely changed the level of H2S in PVN on hemodynamic andsympathetic nerve activityThe bilateral PVN microinjection of H2S donor NaHS, H2S precursor L-Cysteine, CBSinhibitor AOA and CBS agonist SAM. The changes of MAP and RSNA were observedafter microinjection.4The effect of oral administration of L-Cysteine on hemodynamic andsympathetic nerve activityThe rats were randomly divided into six group: Control group, CIH group,Control+L-Cysteine group and CIH+L-Cysteine group, each group has20rats. Rats ofControl and CIH group were free access to water everyday, however, the rest groupswere given distilled water by intragastric administration daily until the last day ofchronic intermittent hypoxia. To find the changes in hemodynamic and sympatheticnerve activity after oral administration of H2S precursor L-Cysteine.5Effects of oral administration of L-Cysteine on the level of H2S in PVNGENMED organization colorimetric quantification assay kit was used to measured thelevel of H2S, to observe the changes of H2S level in PVN after long-term elevated H2Scontent by oral administration of L-Cysteine.6Effects of oral administration of L-Cysteine on the activity of CBS and CSEUsing ELISA kits to detect the activity of CBS and CSE in PVN of Control group andCIH rats after long-term elevated H2S content by oral administration of L-Cysteine. Results1CIH could induce blood pressure elevation and sympathetic nervous overactivity inrats.2The level of H2S in the PVN in CIH rats were significantly decreased than those incontrol rats, along with increased CBS activity.3Microinjection of a H2S donor NaHS or the precursor L-Cysteine into the PVNdecreased MAP and RSNA in both CIH rats and control rats, this response wassignificantly augmented in CIH rats. AOA, the CBS inhibitor, increased MAP andRSNA in Control group, but had no effect on CIH roup. In contrast,, microinjection ofthe CBS agonist SAM decreased MAP and RSNA in CIH group not Control group.4CIH induced the increase in blood pressure and sympathetic activity was inhibitedafter oral administration of L-Cysteine to increased H2S, but it was failed to recover tonormal.5CIH induced the decrease in H2S level was evaluated after oral administration ofL-Cysteine to increased H2S, but it was failed to return to normal.6CIH induced the decrease in CBS activity was evaluated after oral administration ofL-Cysteine, but it was failed to return to normal.Conclusions1The decreased H2S in PVN involved in CIH induced blood pressure elevation andsympathetic nervous overactivity,in rats.2Oral administration of L-Cysteine significantly inhibited CIH induced-hypertensionand sympathetic nervous overactivity, which might be associated with elevated levels ofH2S in PVN.