The Correlation And Mechanism Between Blood Pressure Variability And Vascular Function

Part one.Correlation between ambulatory blood pressure variability and vascular function in middle-aged normotensive individualsObjective:Recently,a series of cross-sectional and longitudinal studies have shown that short-term BPV correlates closely with target organ damage and the incidence of cardiovascular events in hypertensive patients.However,without the background of hypertension,whether can BPV independently affect target organ damage?Therefore,the purpose of this study was to investigate the association between ambulatory blood pressure variability(ABPV)and vasodilator function in a cohort of putatively healthy middle-aged normotensive individuals.Furthermore,it may be expected to discover as early as possible warning indexes of blood pressure available for predicting cardiovascular risk for middle-aged normotensive population and to offer basis for early intervention.To the best of our knowledge,our study was the first to report on the relationship between measures of vasodilator function and ABPV in middle-aged normotensive population.Methods:Cross-sectional study of 285 randomly selected 40-59 years old normotensive participants who underwent 24-hour ambulatory blood pressure monitoring and brachial artery ultrasound assessment.Systolic and diastolic BPV of 24-hour,daytime and nighttime were calculated using the coefficients of variation(CV)and the average real variability(ARV).Brachial arterial endothelium-dependent vasodilation(EDD)was assessed in response to increased flow and endothelium-independent vasodilation(EID)was assessed in response to nitroglycerin.Relationships were explored using univariate and multivariate linear regression.Results:Our results showed that The%EDD were negatively associated with the CV of 24-hour SBP,the ARV of 24-hour SBP and DBP in univariate analysis.However,the CV and ARV of 24-hour SBP remained significant and independent associated with%EDD in multivariate analysis.Additionally,mean levels of 24-hour SBP and DBP,the CV of 24-hour SBP and DBP,the ARV of 24-hour SBP and DBP,the CV of daytime SBP and the ARV of daytime DBP all were significantly associated with%EID.However,after adjusting for covariates in stepwise multiple regression analyses,higher the CV and ARV of 24-hour SBP,and the ARV of 24-hour DBP remained significant and independent associated with lower%EID.In addition,the coefficient of determination was somewhat greater in multivariable analysis using 24-hour SBPV rather than DBPV.Conclusion:Our results indicated that a higher 24-hour BPV,especially the higher levels of 24-hour SBPV,may independently predict the impairment of endothelium-dependent and-independent vasodilator functions in a middle-aged normotensive population without obvious risk factor for atherosclerotic disease,meaning that this population with high 24-hour BPV deserves more attention than usually ascribed to intervene and prevent vascular complications.Part two.Effects of losartan on vasomotor function and canonical transient receptor potential channels in the aorta of rats with arterial pressure lability induced by sinoaortic denervationObjective:Animal studies found that sinoaortic-denervation(SAD)rats with significant increased Blood pressure variability(BPV)could be investigated without a sustained elevation of BP level.The previous studies have shown that obvious organ damage,including cardiac hypertrophy,vascular remodelling and renal lesions,exists in SAD rats.Considering the adverse effect on the target organ caused by increased BPV,therefore,exploring the molecular mechanisms underlying abnormal BPV induced organ damage and seeking effective therapeutic targets are still one of the hot research topic in the cardiovascular field.To sum up,the current study was designed to observe the effects of treatment with losartan on BPV,vasomotor function and the canonical transient receptor potential(TRPC)channels in SAD rats.Also,the potential mechanisms involved in these effects were preliminarily explored.To the best of our knowledge,our study was the first to report on the role of TRPC1 and 6 channels in SAD rats treated with losartan.Methods:SAD was performed in male Sprague-Dawley rats at the age of 10 weeks.Rats were randomly assigned into three groups(n=12 in each group)as following:(1)sham-operated group(Sham group);(2)sinoaortic-denervated group(SAD group);(3)SAD treated with losartan(SAD+Los group).8 weeks after SAD or Sham surgery,haemodynamic parameters were measured by catheterization in conscious rats,and the coefficient of variance of 24-h mean blood pressure was calculated as metrics of short-term BPV;the thoracic aortic endothelium-dependent vasodilation(EDD),endothelium-independent vasodilation(EID)and vasoconstriction function(VCF)were evaluated by physiological vascular ring tension recording system;and the mRNA and protein expressions of TRPC1 and 6 in endothelial cells(ECs)and smooth muscle cells(SMCs)of thoracic aorta were determined respectively by reverse transcription polymerase chain reaction(RT-PCR)and Western-Blotting.Results:SAD induced increases in 24-hour SBPV and DBPV,enhancements of thoracic aortic VCF,attenuations of EDD,downregulation of TRPC1 and 6 mRNA and protein expression levels in RAECs and upregulation of TRCP1 and 6 mRNA and protein expression levels in RASMCs at 8 weeks after surgery.After the SAD rats were treated with losartan for 8 weeks,24-hour SBPV and DBPV values were decreased,thoracic aortic VCF was reduced,EDD was ameliorated,and TRPC1 and 6 mRNA and protein expression levels were upregulated in RAECs and downregulated in RASMCs.Conclusion:The present study indicated that increased BPV and dysregulation of TRPC1 and 6 were involved in the mechanisms underlying vascular dysfunction in SAD rats,and losartan could be useful for preventing the impairment of vascular function in SAD rats by reducing BPV and regulating the mRNA and protein expressions of TRPC1 and 6.