The Influence of Losartan on ACE2-Ang(1-7)-MAS-ERK Pathway of Hearts in Spontaneously Hypertensive Rats
Meixi Wang · Chinese Journal of Hypertension · 2010
Objective To explore the change of ACE2-Ang(1-7)-MAS-ERK in the heart of spontaneously hypertensive rats and the effect of losartan on this pathway.Methods30-week-old spontaneously hypertensive rats were randomly divided into SHR group (n=11) and losartan group [losartan 30 mg/(kg·d),n=12], and 12 Wistar rats of the same age served as control.After 12 weeks treatment, the level of Ang Ⅱ, Ang(1-7) in serum and myocardial tissue were detected by radioimmunoassay.The mRNA expression levels of ACE, ACE2 and MAS were detected by RT-PCR respectively.The protein levels of ACE, ACE2 and pERK1/2 in left ventricle were detected by the Western blot.ResultsAfter 12 weeks of medication, the blood pressure in losartan group was lower than that in SHR group [(164.3±21.6)vs(241.3±24.5)mm Hg,P0.01].The relative level of myocardial ACE mRNA and protein expression in SHR was significantly higher than WKY group, while the relative expression level of ACE2 mRNA and protein in SHR was significantly lower than the WKY group.The expression of MAS receptor mRNA in SHR group was lower than WKY group.The expression level of ACE2 mRNA and protein in losartan group was higher than that in SHR group.The expression of MAS receptor mRNA in losartan group was higher than SHR(P0.01).The relative level of myocardial pERK1/2 protein in losartan group was lower than the SHR group.ConclusionsThe ratio of ACE/ACE2 was unbalanced in rat of SHR, ACE2-Ang(1-7)-MAS-ERK pathway may play a role in the process of myocardial remodelling in SHR treated by ARB.