| In modern society,obesity has become one of the important factors that seriously affect the health of people.Obesity can result in leptin resistance and insulin resistance,leading to type 2 diabetes,hypertension,coronary heart disease,fatty liver and so on.Obese Zucker rats(OZRs),characterized by obesity and metabolic syndrome(MS),are ideal animal models for obesity and MS research in human being.Arterial baroreflex,including carotid sinus and aortic arch baroreflex,plays a pivotal role in acute regulation of blood pressure.The nucleus tractus solitaries(NTS)is an important relay center for impulse afference of carotid sinus and aortic arch pressure receptors into center and integration of reflex inputs.Based on the inputs,medullary cardiovascular center can adjust the sympathetic and vagal tension,and change the activity of heart and blood vessels to maintain the homeostasis of arterial blood pressure.A large number of studies have proved that attenuated baroreflex will result in hypertension.Chronic intermittent hypobaric hypoxia(CIHH)refers to the intermittent exposure of tissues or body to hypoxic hypoxia,while the rest of time in a normal atmospheric environment.A large number of studies confirmed that CIHH not only has significant cardiac protection,immune regulation,improve metabolism,but also has obvious anti-hypertensive effect.CIHH anti-hypertensive effect may be related to its enhanced central and peripheral nitric oxide(NO)generation,facilitated baroreflex and reduced vascular peripheral resistance.OZRs show an increased arterial blood pressure or borderline hypertension.However,the baroreflex function in OZRs and effect of CIHH on arterial blood pressure and baroreflex in OZRs have not been elucidated.Objective: The aim of this study was to investigate the effect of CIHH on arterial blood pressure and the underlying mechanism in OZRs usingfunctional,electrophysiological and molecular biology methods.Methods: Adult male lean Zucker rats(LZRs)and obese Zucker rats(OZRs)were randomly divided into four groups: LZRs group,LZRs+CIHH group,OZRs group and OZRs+CIHH group.LZRs+CIHH and OZRs+CIHH rats were placed in a hypoxic chamber to experience 28-day hypobaric hypoxia(6 h per day)simulating 5000 m altitude.The feeding environment and diet of LZRs and OZRs rats were same as CIHH-treated rats except for CIHH explosure.Body weight and tail arterial pressure of animals were measured weekly.Arterial blood pressure(BP),heart rate(HR)and renal sympathetic nerve activity(RSNA)in anesthetized rats were recorded by using Powerlab system and LabChart software.RSNA was recorded during BP increase by intravenous injection of phyenylephrine(PE)and decrease by sodium nitroprusside(SNP).The baroreflex function curves and gain curves were plotted with RSNA vs MAP and the differences among groups were analyzed.The protein expression of nNOS,eNOS and iNOS in NTS were measured with Western blot technique.Results:1 Effect of CIHH on body weight of rats Compared with LZRs rats,the body weight of OZRs rats was significantly increased(P <0.01),but decreased in LZRs+CIHH rats(P<0.05).The body weight of OZRs+CIHH rats was significantly lower than that in OZRs rats(P <0.01).The results demonstrated that CIHH could reduce body weight of rats.2 Effects of CIHH on arterial blood pressure of rats Compared with LZRs,the arterial systolic pressure was significantly increased in OZRs rats(P<0.01),and no changed in LZRs+CIHH rats(P>0.05).Compared with OZRs rats,arterial systolic pressure was significantly decreased in OZRs+CIHH rats(P<0.05).The results demonstrated that CIHH treatment has an obvious anti-hypertensive effect in OZRs rats.3 Effects of CIHH on baroreflex RSNA Compared with LZRs rats,the baroreflex RSNA was increased in OZRs rats while decreased in LZRs+CIHH rats.Compared with OZRs rats,the RSNA of baroreflex was significantlyreduced in OZRs+CIHH rats.There was no significant difference of RSNA between OZRs+CIHH and LZRs rats.Compared with LZRs rats,the slope of baroreflex function curve was significantly decreased and shifted to the upper right in OZRs rats,but the slope was increased slightly and shifted to the lower and left in LZRs+CIHH rat.Compared with OZRs rats,the slope of functional curve was significantly increased in OZRs+CIHH rats.Compared with LZRs rats,the baroreflex gain curve was decreased in OZRs rats,P2 value was increased(P<0.01)and the Gmax value was decreased(P<0.01).However,the baroreflex gain curve was lifted in LZRs+CIHH rats,P2 value was decreased(P<0.05)and Gmax value was increased.Compared with OZRs rats,the baroreflex gain curve was shifted upward in OZRs+CIHH rats,P2 value was decreased(P<0.01)and Gmax was increased(P<0.05).The results suggested that the baroreflex sympathetic inhibition was decreased and baroreflex function was impaired in OZRs rats;CIHH could facilitate baroreflex and rescue damage of baroreflex function in OZRs rats.4 Effects of CIHH on baroreflex HR Compared with LZRs rats,slope of BP-HR curve was reduced,shifted to upper and right,and amplitude of?HR was decreased in OZRs rats.Similar to LZRs rats,there was no change of slope of BP-HR curve and amplitude of ?HR in OZRs+CIHH rats.Compared with OZRs rats,slope of BP-HR curve was increased and amplitude of ?HR was increased in OZRs+CIHH rats.Compared with LZRs rats,the BP-HR gain curve was shifted to lower,P2 value was increased(P<0.05),blood pressure value at middle of curve was increased,and Gmax was significantly decreased in OZRs rats(P<0.01).There were no differences of P2 between LZRs+CIHH and LZRs rats.Gmax was decreased in LZRs+CIHH(P<0.05).Compared with OZRs rats,HR was significantly decreased(P<0.05),BP-HR gain curve was shifted to left,P2 value was decreased,the blood pressure at middle curve was decreased(P<0.01)and Gmax value was increased in OZRs+CIHH rats(P<0.05).The results suggested that the baroreflex HR inhibition was impaired in OZRs rats;CIHH could enhance the baroreflex HR inhibition and improve the damage of baroreflex HR inhibition in OZRs rats.5 Effects of CIHH on NOS expression in NTS Compared with LZRs rats,the expression of nNOS,eNOS and iNOS in NTS was significantly decreased in OZRs rats(P<0.05),but increased in LZRs+CIHH rats(P<0.05).The expression of nNOS,eNOS and iNOS in NTS was significantly higher in OZRs+CIHH rats than that in OZRs rats(P<0.05).The results demonstrated that CIHH could upregulate the expression of three kinds of NOS in NTS,and antagonize the downregulation of NOS expression in OZRs.Conclusion: This study demonstrated for the first time that CIHH can facilitate baroreflex and improve the beroreflex damage in OZRs rats through increase of NOS expression and NO production in NTS,which might be one of mechanisms for anti-hypertension of CIHH in OZRs rats. |
PDF Full Text Request