The Effect Of High Blood Press Variability On Thrombus Stability And Hydrogen-rich Saline Intervention

BackgroundHypertension can cause target organ damage of heart,brain and kidney.Although hypertension exposes blood vessels to increased pulsatile stress,thrombotic rather than hemorrhagic events,such as cerebrovascular ischemia and myocardial infarction,represent a major complication in hypertensive patients.Besides thrombogenesis,embolus detachment is another cause of thrombotic events.So,research on embolus detachment is significant for understanding and control of thrombotic disease in hypertension.Thrombus stability affects the fate of thrombosis.When thrombus instability occurs,embolus is easy to shed from thrombosis.Large embolus could block blood vessels and result in thrombotic disease.It has been reported that high blood pressure variability?BPV?enhanced oxidative stress and raised platelet calcium(Ca²⁺)level in rats with sinoaortic denervation?SAD?,while increased platelet calcium level contributed to thrombus instability.So,we hypothesized that high BPV could lower thrombus stability via oxidative stress and increase of platelet Ca²⁺level,and hydrogen could improve thrombus stability though antioxidative stress and decrease of platelet Ca²⁺level.AimsTo investigate the effect of high BPV on thrombus stability and hydrogen intervention.MethodsRats were divided into sham-operated?Sham?group,SAD group,SAD+hydrogen-rich saline group.Except the Sham group,SAD was performed in the other groups.Sham group and the SAD group were injected intraperitoneally with normal saline(10 ml·kg^-1·d^-1)for 8 weeks,when SAD+hydrogen-rich saline group was injected intraperitoneally with hydrogen-rich saline(10 ml·kg^-1·d^-1)for8 weeks.In another experiment,four weeks after SAD,hemodynamic parameters continuously recorded in consciouse unrestrained rats in Sham and SAD group.Blood pressure?BP?and blood pressure variability?BPV?was calculated.Baroreceptor sensitivity was detected.At low shear rate(300s^-1)and high shear rate(1200s^-1),secondary perfusion in a well-defined perfusion chamber was used to measure the decrease rate of fluorescence intensity in adhesion of platelets.The collagen-induced platelet disaggregation was determinated with turbidimetry.Washed platelets adhesion and spreading on fibrinogen was observed.The levels of nitric oxide?NO?and Ca²⁺in washed platelets were determined by flow cytometry.The levels of superoxide dismutase?SOD?,malondialdehyde?MDA?,NO in plasma were determined with turbidimetry.ELISA was used to detect the content of reactive oxygen species?ROS?,glutathione peroxidase?GSH-Px?in plasma.Results1.When compared with the Sham group,SBP,DBP and MBP remained unchanged,while SBPV,DBPV and MBPV were significantly increased,BRS was significantly lower in SAD group.SAD exhibited the feature of high BPV with normal BP.The results indicated that the SAD model was successfully generated.2.Compared with Sham group,the decrease rate of fluorescence intensity in adhesion of platelets,and the disaggregation rat of platelet aggregation induced by collagen was high in SAD group;Additionally,the number of platelet spreading on fibrinogen and the number ratio of platelet spreading to adhesion decreased;Plasma ROS and MDA level in and platelet the Ca²⁺level was significantly higher;The level of NO,SOD and GSH-Px in plasma and the levels of NO in washed platelets was significantly reduced in SAD group.3.Compared with the SAD group,the decrease rate of fluorescence intensity in adhesion of platelets,and the disaggregation rat of platelet aggregation induced by collagen is lower in SAD+hydrogen-rich saline group;Moreover,the number of platelets spreading on fibrinogen and the number ratio of platelet spreading to adhesion increased;Plasma ROS and MDA level and platelet Ca²⁺level was significantly lower;The level of NO,SOD and GSH-Px in plasma and the levels of NO in washed platelets was significantly raised in SAD+hydrogen-rich saline group.Conclusion1.High BPV could reduce the thrombus stability.The mechanism may be involved in oxidative stress and increased level of Ca²⁺in platelets.2.Hydrogen could improve thrombus stability with high BPV.This effect may be related to antioxidative stress and decreased level of Ca²⁺in platelet.