Angiotensin 1-7 attenuates left ventricular remodeling in deoxycorticosterone acetate salt hypertensive rats / 中国药理学通报

ABSTRACT

Aim To investigate the effect of angioten-sin 1-7 (Ang 1-7 )on the cardiac hypertrophy and my-ocardial fibrosis in deoxycorticosterone acetate (DOCA)-salt hypertensive rats and its possible mecha-nism.Methods Male Sprague-Dawley rats were used to establish DOCA-salt hypertensive model,which un-derwent uninephrectomy surgery and were subcutane-ously injected with a DOCA,and replaced drinking water with 1% saline solution for 4 weeks.DOCA-salt animals were implanted with osmotic minipumps, which delivered Ang 1-7 chronically for 4 weeks (200 ng ·kg-1 ·min-1 ).Arterial blood pressure,left ven-tricular function in rats,the area of myocardial cells in HE stained specimens,and the area of myocardial fi-brosis Sirius red staining specimens were measured. Real time PCR was used to detect the expression of at-rial natriuretic factor (ANF ) and β-myosin heavy chain (β-MHC)mRNA in heart,and TGF-β1 protein expression was observed by Western blot in myocardial tissue.Results In the first week,DOCA salt rat had a significant increase in arterial blood pressure,and reached a peak in the fourth week;while the left ven-tricular end-systolic pressure (LVESP),left ventricu-lar end-diastolic pressure (LVEDP ) and ventricular contraction the maximum rate of pressure rise (+dp/dt)had also undergone significant changes in DOCA salt rats. After chronic infusion of Ang 1-7 for 4 weeks,the arterial pressure,LVESP and LVEDP were significantly reduced and +dp/dt were increased sig-nificantly in DOCA salt rats (P<0.05 ,n=7 ).Ang 1-7 significantly reduced the cardiac index and myocar-dial cell area,as well as the up-regulated expression of ANF and β-MHC mRNA in DOCA salt rats (P <0.05 ,n =7 ).Meanwhile,Ang 1-7 also significantly decreased the perivascular fibrosis and interstitial fibro-sis area, and significantly inhibited the increase of TGF-β1 expression in DOCA salt rats (P<0.05 ,n=7 ).Conclusion These results indicate that Ang 1-7 has a cardioprotective effects through reducing arterial pressure and improving cardiac fibrosis and hypertro-phy in the DOCA-salt model of hypertension.