Passive Leg Movement Attenuates Endothelial Dysfunction In Rat Model Of Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction.is a common clinical syndrome,and the hospitalization rate is increasing year by year.So far,no effective treatment for HFpEF has been found,and the pathophysiology of HFpEF is complex and diverse.It is still unknown that vascular endothelial dysfunction,as a new pathophysiological mechanism for heart failure with preserved ejection fraction,may become a new target for the treatment of heart failure with preserved ejection fraction.In recent years,a large number of studies have shown that exercise can increase the activity of vascular endothelial nitric oxide synthase,further enhance endothelium-dependent vasodilation,and exercise plays a very beneficial role in cardiovascular disease.Related research reports indicate that there is a close relationship between vascular endothelial dysfunction and HFpEF exercise intolerance,and exercise intolerance is mainly reflected by cardiopulmonary exercise test and VO2 peak.Exercise training increased VO2 peak and body function scores in patients with HFpEF.Exercise training can benefit from improving vascular function such that peak VO2 changes cause exercise intolerance.In the previous study,we found that passive leg exercise can improve the cardiac function of heart failure with preserved ejection fraction.The aim of this study was to establish a rat model of heart failure with preserved ejection fraction to further explore whether passive leg exercise can improve endothelial function.Endothelial dysfunction may be an important mechanism leading to system-wide adverse reactions.Therefore,treatment for endothelial dysfunction is expected to become a future therapeutic target for HFpEF Background:Heart failure patients with preserved left ventricular ejection fraction(HFpEF)have endothelial dysfunction,but the underlying molecular mechanisms remain unknown.In addition,whether exercise training improves endothelial function in HFpEF is still controversial.Objective:To assess the effects of passive leg movement on the function and molecular alterations in the endothelium associated with HFpEF.Methods and ResultsMale Dahl salt-sensitive rats were randomized for 7 wk into the following groups: 1)(NS)normal salt :(0.4% NaCl;)2)(HS)High salt:(8% NaCl);and 3)(HS+PLM)Passive leg movement group:(8% NaCl),4)(HS+ISO)Isoflurane as Positive control group :(8% NaCl),;HS+PLM and HS+ISO groups rats were fed a high-salt diet for 13 weeks,and randomized to receive passive leg movement or Isoflurane.Echocardiography and invasive hemodynamic measurements were used to assess diastolic dysfunction.Endothelial function of the vascular was measured in vitro.PLM significantly and comparably improved vascular endothelium dependent relaxation to acetylcholine,aorta remodeling,and eNOS dimer disruption of DS rats,PLM also reduced expression of vascular p22 phox levels,and expression of p-eNOS/eNOS..Conclusion:.In the HFpEF model established by Dal salt-sensitive rats,we found that endothelium-dependent vasodilation was impaired,and that non-endothelium dependent diastolic function did not change.PLM can improve endotheliumdependent dilation,which may be related to the synergistic attenuation of vascular fibrosis and oxidative stress,and may also be related to decreased expression of eNOS.