| BackgroundObstructive sleep apnea (sleep apnea obstructive, OSA) is closely associated with hypertension, which is considered to be an independent risk factor for hypertension and cardiovascular disease. Sleep disruption and chronic intermittent hypoxia (CIH) are regarded as significant damage mechanisms of obstructive sleep apnea syndrome (OSAS) patients. hydrogen sulfide (H2S), as an important gas signal molecule and vasodilator, has been demonstrated the significant biological roles of endogenous production and exogenous adjustment.There is a new field of improving the balance of vascular homeostasis and vasodilatation. It has been reported that H2S plays a significant effect on hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries, and participates in vascular protection and regulation. Meanwhile, H2S plays a dramatic role in anti-inflammation, suppressing oxidative stress, promoting cell proliferation and apoptosis. It plays an important role in the cardiovascular system, especially in the formation of hypertension.Objective1 To study the effect and mechanism of H2S on the vascular function of thoracic aorta in chronic intermittent hypoxia rats.2 To observe the preventive effects of H2S donor NaHS on chronic intermittent hypoxia induced hypertension, and provide experimental evidence for the prevention and treatment of OSAS induced complications.MethodsMale SD rats were randomly divided into control (sham) group and chronic intermittent hypoxia (CIH) group, the conscious noninvasive method with tail cuff was measured tail systolic blood pressure (SBP). The experiment of vascular tension in vitro was carried out to observe diastolic and systolic effects on thoracic aorta rings. Western blot was applied to measure protein expressions of cystathionine-γ-lyase (CSE) in blood vessels and ATP sensitive potassium (KATP) channel subunits Kir6.1 in vascular smooth muscles. H2S content in blood vessels and plasma were measured by ELISA. Immunohistochemistry was used to measure the protein expression of Kir6.1 in vascular smooth muscle.1 Animal models of chronic intermittent hypoxiaMale SD rats were randomly divided into three groups:control (sham) group, chronic intermittent hypoxia (CIH) group and CIH+NaHS group. CIH group was dealt with chronic intermittent hypoxia for 28 days, and sham group was exposed to sham conditions (air to air cycles). CIH+NaHS group was injected intraperitoneally with NaHS every day. The monitoring index of successful animal models was that SBP was equal to or greater than 160 mmHg.2 The changes of H2S content in thoracic aorta and plasma were measured by ELISA The changes of H2S content in thoracic aorta were measured by ELISA in sham and CIH group. The treatment effects of NaHS were observed on plasma level of H2S. The changes of CSE protein expression in blood vessels were detected by Western blot in sham and CIH group.3 The experiment of vascular tension in vitroMale SD rats were randomly divided into sham group and CIH group, the changes of vascular tension were observed in thoracic aorta precontracted with PE when cumulative concentrations of NaHS were applied in sham group and CIH group, respectively. Pretreament with KATP channel inhibitor glibenclamide before cumulative concentrations of NaHS were applied, the changes of vascular tension were observed in thoracic aorta precontracted with Phe.4 KATP protein expression in vascular smooth muscle was measured by western blot and immunohistochemistryThe changes of CSE protein expression in blood vessels and KATP protein expression in vascular smooth muscle were measured by western blot, KATP protein expression in vascular smooth muscle was measured by immunohistochemistry.Results1 CIH could induce the decrease of H2S content and the protein expression of CSE in rat thoracic aorta.2 CIH could induce the diastolic and contractile dysfunction in rat thoracic aorta.3 In endothelium-intact arteries precontracted with Phe, compared with sham arteries, contraction of NaHS at low concentrations was enhanced and relaxation of NaHS at high concentrations was reduced in CIH arteries. In endothelium-denuded arteries precontracted with Phe, relaxation of NaHS at high concentrations was decreased both in sham and CIH group.4 The vasodilatation induced by NaHS was caused partially by the open of KATP channel in sham and CIH arterial rings.5 Long-term application of NaHS could reduce the blood pressure of rats induced by CIH, enhance the level of H2S in plasma and protein expression of KATP in vascular smooth muscle by CIH-induced hypertension rats.Conclusions1 CIH could induce the diastolic and contractile dysfunction in rat thoracic aorta, and the mechanism may be related to the decrease of endogenous H2S and abnormal vascular reaction to H2S. Contraction of H2S at low concentrations was enhanced and relaxation of H2S at high concentrations was reduced in CIH arteries2 Long-term application of H2S donor NaHS can significantly inhibit CIH induced-hypertension, at the same time,the inhibitory effect may be related to the increased H2S level in plasma, and maybe up-regulate vascular smooth muscle KATP protein expression to enhance its vasodilatation. |
