Probing The Potential Role Of Baroreflexes In The Long-term Regulation Of Blood Pressure

Background: Baroreflex has been verified play an important role in the short-term blood pressure(BP)regulation,yet whether it also participates in long-terms BP control is still having a lot of debates.The pioneer study demonstrated baroreflex only played a key role in maintaining BP in a relatively short period and contributed nothing to the long-term BP regulation.However,this dogma faced many challenges since 2000 s.Especially since baroreceptor activation therapy(BAT)reached a series of success in the treatment of resistant hypertension,more and more researchers began to realize baroreflex might also play a role in the long-term BP regulation.But the actual mechanism remained unclear.To elucidate the neurogenic mechanisms underlying the pathophysiology of the long-term BP control,thus providing the theoretical basis for the BAT,we conduct the following 3-part research.Object: Part I: investigate the baroreflex function in multi-strains rats,including Spontaneously Hypertensive rats(SHR),Wistar Kyoto(WKY)rats,Sprague Dawley rats(SD),Dahl Salt-Sensitive rat(SS)and Dahl SaltResistant rat(SR).Part II: investigate the potential mechanism underlying the abnormal baroreflex function in the SHR/WKY rats.Part III: evaluate the translational value of the results and conclusions from the previous 2parts.Method: Part I: Animal experiments and computational analysis.We used ultrasound measure arterial mechanics and telemetry to measure the BP waveform.We develop a new algorithm to evaluate baroreflex function and bring a new index called on fraction to quantify the results of algorithm analysis.This index indicates the time fraction when baroreflex participates in the BP regulation.Part II: Animal experiments.We use sinoaortic denervation(SAD)surgery to investigate the potential role of baroreflexes in the long-term BP regulation in the SHR/WKY rats.We also do behavior analysis and exercise training.By applying the stimulus of intermittent hypoxia and hypercapnia,we observed the parameters of cardiovascular systems and measured the activity of the carotid sinus nerve(CSN).Part III: translational study.By applying Lasso regression in 24 patients,we investigated the possibility of translating our algorithm form rats to human.Results: Part I: 1)the on fraction is decreasing with aging;2)the on faction and the mean arterial pressure are negatively correlated;3)when the baroreflex is on,the average level and variability of MAP is lower compared to when the baroreflex is off;4)MAP the tends to decrease during the on state and tends to increase during off state.All the above phenotypes are only happened in the SHR/WHY strain but not in other rat strains.Part II: 1)the BP was chronic increasing in the WKY-SAD rats but not in the SHR-SAD rats;2)exercise,hypoxia and hypercapnia can lower the on fraction of SHR and WKY rats but not SD rats;3)chemoreflex overactivation can suppress the afferent of the baroreceptor in the SHR rats but not in SD rats.Part III: 1)the result of algorithm is reproducible;2)the on fraction in patients who have hypertension medical history is lower compared to patients who do not have;3)patients with acidosis’ s on fraction is lower;4)on fraction has the potential to predict the incidence of acidosis.Conclusions: From all mentioned above,we draw the following conclusions: 1)baroreflex can contribute to the long-term BP regulation via the way of interacting with chemoreflex;2)the SHR rat should be used as an animal model of secondary neurogenic hypertension.The etiology of the hypertension in the SHR rat is chemoreflex override the baroreflex,causing sympathetic overdrive,thus elevating the BP level;3)the selfdeveloped algorithm shows a good prospect of clinical translation,and it may be helpful for the diagnosis and treatment of hypertension and other diseases in the future.