The Role Of CaCCs/TMEM16A In The Aerobic Exercise-induced Regulation Of Vascular Tension Of Mesenteric Arteries In Hypertensive Rats

Research purposes:the primary hypertension is one of clinical common chronic diseases.Endothelium dependent vasodilatation function is impaired when hypertension occurs,in response to the tube cavity pressure rising,vascular smooth muscle cells(VSMC)arise pathological changes.Calcium-activated chloride channels(CaCCs)refers to the activation of calcium chloride ion channels,it is widely expressed in vascular smooth muscle,its open cause CI~-outflow,the cell membrane depolarization,making the vasoconstriction.The present study suggests that TMEM16A protein in the rat VSMC controls artery vasoconstriction and maintains blood pressure levels,and TMEM16A protein is proved to exist in the mesenteric artery.Long term aerobic exercise training can induce the body a series of adaptive change from the level of cells,tissues and organs.In recent years,the contacts of sports and vascular ion channels are increasingly attention by all of us.However,there are still many unknown part in long-term exercise on the ion channel of the reconstruction of the pathological effects of high blood pressure.This experiment through the aerobics SHR rats mesenteric arteries tension measurement and the main protein CaCCs TMEM16A expression detection,specific TMEM16A protein expression and its change rule of the impact on the function of vascular smooth muscle contraction,to further elaborate aerobic exercise regulation mechanism of blood vessel function in patients with high blood pressure,so that aerobic exercise can better application field of mass fitness.Methods:choose 12 weeks of male spontaneously hypertensive rats(SHR,n=24)and age male rats blood pressure normal control group(WKY,n=24).WKY group and SHR group were randomly divided into 2 groups:quiet control group(WKY-SED,n=12;SHR-SED,n=12)and aerobic exercise group(WKY-EX,n=12;SHR-EX,n=12).Exercise group is for 12 weeks to treadmill exercise(20 m/min,60min/d,5 d/w).Quiet group is for free diet,no exercise intervention.Before and after the exercise training,measure every group with basic indicators,including body weight(BW),heart rate(HR)and systolic blood pressure(SBP).After 12 weeks,each group of rats mesenteric arteries(level 2),in vitro preparation of mesenteric artery rings,with the determination of each group of norepinephrine(NE)and specific T16Ainh-A01's reactive changes.By Western Blot method to detect TMEM16A protein expression of mesenteric artery organization in each group.Results:1)Before aerobic exercise,compared with WKY-SED group,there is no significant difference between SHR-SED group weight(P>0.05),systolic blood pressure increased significantly(P<0.05).After 12 weeks of aerobic exercise,compared with SHR-SED group,systolic blood pressure and weight of SHR-EX group was obviously lower(P<0.05);Compared with WKY-SED group,the weight and systolic blood pressure of WKY-EX group has a downward trend(P<0.05).2)each group of 60mM KCl reaction,there is no significant difference between the vascular tension,after joining NE,SHR-SED group'microvascular contraction had a significantly higher reactivity than WKY-SED group(P<0.05).After 12 weeks of aerobic exercise,compared with SHR-SED,SHR-EX mesenteric artery contraction reactivity decreased significantly(P<0.05).3)T16Ainh-A01 can cause NE inducing mesenteric arterial vasodilation.After T16Ainh-A01 was added,the vasomoconstrictive reactivity of the mesenteric artery in the SHR-SED group was significantly higher than that in the WKY-SED group(P<0.05).After 12 weeks of aerobic exercise,compared with the SHR-SED group,the SHR-EX group showed significantly lower mesenteric artery relaxation response(P<0.05).Exercise can significantly reduce SHR T16Ainh-A01 rat mesenteric artery vascular reaction(P<0.05).4)By Western Blot method to detect TMEM16A protein expression in the groups of mesenteric artery organization,the results showed that compared with WKY-SED group rats,SHR-SED groups of mesenteric artery TMEM16A protein expression significantly increases,the difference was statistically significant(P<0.05),and after aerobic exercise,TMEM16A protein expression of SHR rats decreased(P<0.05),the WKY-EX group TMEM16A protein compared with WKY-SED group has also dropped,but is not obvious.Research conclusions:aerobic exercise can significantly reduce the systolic blood pressure of hypertension rats,which may be related to inhibiting TMEM16A protein expression increased,thereby reducing substances of the sensitivity of the arteriole to shrink blood vessels.