自发性高血压大鼠MnPO注射AngⅡ对EDLS释放和近球小管Na^+,K^+-ATPase活性的影响

Effect of MnPO microinjection of Ang Ⅱ on endogenous digitalis-like substance release Na^+,K^+-ATPase activity of proximal tubule in SHR

目的探讨自发性高血压大鼠(SHR)正中视前核(MnPO)注射AngII对血清内源性洋地黄样物质和肾脏近球小管Na+,K+-ATPase活性的影响。方法24只雄性SHR随机分为人工脑脊液组、AngⅡ组、Losartan组,同时选用8只雄性WHY大鼠作为正常对照组。用小动物脑立体定位仪在MnPO区定位并中枢微量注射,放射免疫法测定血清内源性洋地黄样物质(EDLS)和血浆AngⅡ水平,立体显微镜下手工微分离近球小管,液体闪烁计数器测定近球小管管周膜上的Na+,K+-ATPase的活性。结果①MnPO注射AngII后,SHR各组与WHY组比较,血浆AngⅡ水平、血清EDLS水平、近球小管Na+,K+-ATPase的活性有显著性差异(P<0.05)。②MnPO注射AngII后,SHR-AngⅡ组与SHR-人工脑脊液组比较,血浆AngⅡ水平无显著变化(P>0.05),血清EDLS水平显著升高(P<0.05),近球小管Na+,K+-ATPase的活性显著下降(P<0.05)。③在MnPO预先用Losartan处理后,SHR-Losartan组与SHR-AngⅡ组比较,血浆AngⅡ水平无显著性改变(P>0.05),血清EDLS水平明显低于SHR-AngⅡ组(P<0.05),其近球小管Na+,K+-ATPase的活性明显高于SHR-AngⅡ组(P<0.05)。④MnPO注射AngⅡ后,SHR-AngⅡ组血清EDLS水平与其近球小管Na+,K+-ATPase活性呈显著负相关(r=-0.795,P<0.01)。结论在SHR中,AngⅡ在MnPO的AT1受体介导下,引起高水平EDLS释放,从而抑制近球小管Na+,K+-ATPase活性的作用可能与SHR本身调节机制上调有关。

Obiective To study the effect of median preoptic nucleus （MnPO）mieroinjection of Ang Ⅱ on endogenous digitalis-like substance （EDI-S）retease and Na^＋,K^＋-ATPase activity of proximal tubule in spontaneously hypertensive rats （SHR）. Methods 24 male SHR were randomized into Artificial cerebrospinal fluid group （SHR-C group）,Angiotensin Ⅱ group （SHR-A group）, Losartan group （SHR-L group） o 8 male WKY rats were regarded as normal group （WKY group）. Studies were performed on anesthetized SHR and MnPO microinjection were carried out on the accurate site in the rat brain through a sterotaotic apparatus. EDLS and Ang Ⅱ levels in plasm or serum were assessed by radioimmunassay （RIA）. The single proximal tubules were microdissected by free hand and the Na ＋ ,K ＋-ATPase activity in proximal tubules was determined with a micromethod that measured direvty labeld phosphate release by the hydrolysis of [γ-^33p]ATP. Results After MnPO microinjection Ang Ⅱ ,the plasma Ang Ⅱ level,serum EDLS level and the proximal tubules Na^＋,K^＋-ATPase activity in all SHR groups were significantly changed than those WKY group （P〈0.05）.Compared with SHR-C group,the plasma Ang Ⅱ level was not significantly changed in SHR-A group （P〉0.05）, the serum EDLS level in SHR-A group was obviously increased than SHR-C group （P〈0.05）and the proximal tubules Na^＋,K^＋-ATPase activity was significantly decreased than SHR-A group（P〈0.01 ）o In SHR-A group, there was a negative linear correlation between the serum EDLS level and the promimal tubule Na^＋,K^＋-ATPase activity （r=-0.795,P〈0.01）. Pretreatment with losartan in SHR-L group,the plasma Ang Ⅱ level was not significandy changed than SHR-A group （P〉0.05）,the serum EDLS level was obuiously decreased than SHR-A group （P〉0.05）, the promimal tubule Na^＋,K^＋-ATPase activity was markedly higher than SHIR-A group （P〈0.05）. Conclusions The present investigation suggest the Ang Ⅱ may stimulate and modulate hige level EDLS release,inhibit Na^＋,K^＋-ATPase activity in the proximal tubule via MnPO AT1 receptors relation of the up-regulation mechanism in SHR.