Effects of Losartan on Na~+, K~+-ATPase in Proximal Tubules Epithelial Cells of Spontaneously Hypertensive Rats
|School||Zunyi Medical College,|
|Keywords||Losartan Spontaneously Hypertensive rats Roximal Tubules Epithelial Cells Na~+，K~+-ATPase Endogenous Ouabain|
Objective:The present study is designed to investigate the effects of losartan on the activity and expression of Na+, K+-ATPase in the proximal tubules epithelial cells of spontaneously hypertensive rats(SHR), and to understand the relationship between the effects above-mentioned and that of depression.Methods:12 male SHRs 10 weeks after birth (body weight:140±17g) were randomly divided into intragastric administration with losartan group (SHR-L group,30mg. kg-1. d-1,n =6) and with same volume of solvent group (SHR-N group, n= 6). The homologous to the same age with normal blood pressure in male rats (Wistar Kyoto rats, WKY, n= 6) as a control group were intragastric administrated with same volume of solvent. The datas of systolic blood pressures were measured in all animals with tail cuff weekly. All animals were executed under anesthesia 8 weeks after intragastric administration. The samples of blood and the kidneys were acquired. The plasma angiotensinⅡ(AngⅡ) and serum levels of endogenous ouabain (EO) were detected with radioimmunoassay. The renal cortical tissues were to be select,and it’s expressions of Na+, K+-ATPaseα1 subunit mRNA were measured with RT-PCR method. The segments of proximal tubule were isolated and obtained by hand under an stereo microscope, and the Na+, K+-ATP activity of the segments was detected with liquid scintillation.Results:①The systolic blood pressure in the animals of WKY group were always normal and steady during 8 weeks in intragastric administration. The systolic blood pressure in the animals of SHR-N group was always higher significantly than that in WKY group. That in SHR-L group was significant higher that in WKY group first week after intragastric administration but there was not significant difference with SHR-N group (P>0.05) Systolic blood pressure in SHR-L group was significant lower than that in SHR-N group during second week to eighth week after intragastric administration.②The plasma AngⅡlevels in SHR-N group (317.13±83.01 pg.ml-1) was significantly higher than that in WKY group (180.61±50.02 pg.ml-1, P<0.05). That in SHR-L group (466.77±71.61 pg.ml-1) was respectiv significant higher than WKY group (P<0.01) and than SHR-N group (P<0.05).③The serum level of EO in the rats of SHR-N group (175.28±19.63 pg.ml-1) was significant higher than that in WKY group (104.33±17.25 pg.ml-1, P< 0.01).That in SHR-L group (169.76±18.26 pg.ml-1) was higher than that in WKY group, but there was not significant difference with SHR-N group (P>0.05).④The Na+,K+-ATPase activity in proximal tubular in SHR-N group (928.43±100.96 pmolPi.mm-1.h-1) was significantly lower than that in WKY group (1401.70±103.27 pmolPi.mm-1.h-1, P<0.01). That in SHR-L group (1200.63±75.14 pmolPi.mm-1.h-1) was lower than that in WKY group, but there was not significant difference with SHR-N group (P>0.05).⑤Compared with WKY, SHR-N group and SHR-L group of Na+, K+-ATPase subunit mRNA expression was significantly increased, respectively,2.01 and 1.56 times the expression was statistically significant (P=p<0.01 and p<0.05); and compared to SHR-N group, SHR-L group of Na+, K+-ATP enzymeα1 subunit mRNA expression decreased significantly (p<0.05).Conclusion:①Effect of losartan on blood pressure of SHR is reduced significantly, it is also accompanied to circulating blood in the compensatory increase in AngⅡ;②The proximal tubular Na+, K+-ATPase activity of SHR is decreased, one of the reason may be due to Endogenous Ouabain(EO) release of more Palestinian;③The proximal tubular Na+, K+-ATPase activity of SHR is not affected by Losartan and its may be due to increased release of Endogenous Ouabain(EO);④The proximal tubular Na+, K+-ATPase activity of SHR was significantly enhanced, which may lead to sodium overload factor in SHR;⑤The proximal tubular Na+, K+-ATPase enzymeα1 subunit mRNA expression of SHR is reduced significantly by Losartan, and its depression effect may be relevant.