A Study On Protective Effects Of Ang-(1-7) On Kidney And Its Mechanisms In Hypertensive Rats

Background & Objective: Protection of target organ is an important subject in researches of prevention and treatment of hypertension. Renal damages resulting from hypertension are mainly glomerular sclerosis, renal interstitial fibrosis and intrarenal vascular sclerosis. Renal fibrosis is caused by accumulation of improper connective tissues (including interstitial collagen, fibrotic connexin and some glucoproteins) to result in changes of renal structure. As a result, the renal function losses. Renal fibrosis is the common process to develop into renal failure for almost all the renal diseases. Meanwhile, it is not only the common result of various renal damages but also the pathogenic mechanism of progressive destruction of renal unit. It is mainly inhibited as glomerular sclerosis, renal interstitial fibrosis and intrarenal vascular sclerosis. Based on its researches, Eddy concludes that the renal fibrosis is the result of increase in synthesis of extracellular matrix (ECM) protein and inhibition of degradation of the matrix. Nowadays, studies on renal protection mainly focus on prevention and treatment of glomerular sclerosis, renal interstitial fibrosis and intrarenal vascular sclerosis etc. Amongst these studies, the one focusing on reducing excessive accumulation of ECM is the major subject.Ang-(1-7) is a new member of RAS with biological activity. It is reported that Ang-(1-7) has the effects of dilating blood vessels, reducing blood pressure, diuresis, natriuresis, regulating balance among water, salt and electrolytes as well as anti-proliferation. These might be done through antagonizing effects of Ang II, inhibiting activity of ACE and affecting such vaso-active substances as BK, NO and PG etc. These results suggest that RAS has not only Ang II, an important substance that damages hypertensive target organs, but also Ang-(1-7), an important substance that protect the hypertensive target organs. That is to say,Ang-(1-7) might exert protective effects on renal damage caused by hypertension (especially by high-level Ang II). The mechanism might be: 1) Ang-(1-7) can diastolize blood vessels to directly decrease blood pressure and reduce renal damage by hypertension; 2) The renal damage caused by hypertension (including glomerular sclerosis, renal interstitial fibrosis and intrarenal vascular sclerosis) is the result of increase in ECM synthesis induced by proliferation of renal cells (mesenteric cells, interstitial fibroblasts, perivascular cells and renal tubular epithelial cells). Theoretically speaking, the anti-proliferation effect of Ang-(1-7) can reduce renal damage by hypertension.In this study, the technique of implantation of micro-osmotic pump was used to: 1) observe in vivo the protective effects of Ang-(1-7) on kidney after hypertension and its intensity; 2) determine mechanism of the protective effects so as to provide new orientation for development of new drugs for hypertensive target organs and its treatment in clinical practice. Methods & Technical Route:1. Animal model establishment and animal grouping: The models of 2K1C hypertension and INAC hypertension were established in rats. The rats were divided into 5 groups: group A-sham-operated group; group B-2K1C group; group C-2K1C+ Ang-(1-7) group (In group C1, 2K1C and implantation of micro-osmotic pump were simultaneously conducted and the animals were killed on the 14th day after the operation. In group C2, the implantation of micro-osmotic pump was done 14 days after 2K1C and the animals were killed on the 42nd day); group D-INAC group; group E-INAC+ Ang-(1-7) group (In group E1, INAC and implantation of micro-osmotic pump were simultaneously conducted and the animals were killed on the 14th day after the operation. In group E2, the implantation of micro-osmotic pump was done 14 days after INAC and the animals were killed on the 42nd day). These were performed to investigate the preventive and therapeutic effects of Ang-(1-7) intervention for 14 days and 28 days on hypertension in rats and determine their protectivein...