Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus （DM）. It has been known that renin-angiotensin system （RAS） blockers have a renal protective effect. This study aimed to inves...Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus （DM）. It has been known that renin-angiotensin system （RAS） blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin Ⅱ receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin （STZ）-induced DM rats.Methods DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment （OLM＋DM） group. The normal group （non-DM） were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate （GFR） relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated： slope of flow-pressure （minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature）, slope of pressure-GFR （glomerular filtration capacity against pressure）and threshold pressure for beginning filtration at pressure-GFR （preglomerular to postglomerular vascular resistance ratio）. Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.Results The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight,urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM＋DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats （P 〈0.05）. But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats （P 〈0.05） with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan （P 〈0.05）. Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats （P 〈0.05）.The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.Conclusions Treatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.展开更多
Background As the incidence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a crucial objective in the near future. Several studies have shown angiotensin receptor blockers ...Background As the incidence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a crucial objective in the near future. Several studies have shown angiotensin receptor blockers （ARBs） may contribute to the prevention of new-onset type 2 diabetes. This study was conducted to determine if ARBs as monotherapy or combination therapy may experience a decreased incidence of new-onset type 2 diabetes and prevent cardiovascular events. Methods Relevant experimental and clinical studies were identified by searching MEDLINE （1969 to May 30, 2011） to extract a consensus of trial data involving the effect of ARBs on prevention of new-onset type 2 diabetes and cardiovascular events. Studies were included if they were randomized controlled trials versus placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Results Eleven trials were identified, including 82738 patients. ARBs prevented new-onset type 2 diabetes （odds ratio 0.8 （95% CI 0.76, 0.85））. Regardless of indication for use, essential hypertension （seven trials）, impaired glucose tolerance （one trial）, cardiocerebrovascular disease （two trials） or heart failure （one trial）, reductions in new-onset type 2 diabetes were maintained （0.75 （0.69, 0.82）, 0.85 （0.78, 0.92）, 0.80 （0.76, 0.85） and 0.80 （0.64, 0.99）, respectively）. No statistical heterogeneity was observed for any evaluation. However, ARBs did not significantly reduce the odds of all-cause mortality, myocardial infarction and heart failure versus control therapy among all of these studies. But ARBs did reduce the odds of cardiac death and heart failure among the heart failure study versus control therapy. Conclusion ARBs have significant ability to reduce risk of developing new-onset type 2 diabetes but does not improve cardiovascular outcomes over the study follow-up periods among all of included studies.展开更多
文摘Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus （DM）. It has been known that renin-angiotensin system （RAS） blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin Ⅱ receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin （STZ）-induced DM rats.Methods DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment （OLM＋DM） group. The normal group （non-DM） were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate （GFR） relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated： slope of flow-pressure （minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature）, slope of pressure-GFR （glomerular filtration capacity against pressure）and threshold pressure for beginning filtration at pressure-GFR （preglomerular to postglomerular vascular resistance ratio）. Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.Results The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight,urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM＋DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats （P 〈0.05）. But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats （P 〈0.05） with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan （P 〈0.05）. Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats （P 〈0.05）.The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.Conclusions Treatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30971240）. The authors have no conflict of interest to declare.
文摘Background As the incidence of type 2 diabetes is rapidly increasing, prevention of the disease should be considered as a crucial objective in the near future. Several studies have shown angiotensin receptor blockers （ARBs） may contribute to the prevention of new-onset type 2 diabetes. This study was conducted to determine if ARBs as monotherapy or combination therapy may experience a decreased incidence of new-onset type 2 diabetes and prevent cardiovascular events. Methods Relevant experimental and clinical studies were identified by searching MEDLINE （1969 to May 30, 2011） to extract a consensus of trial data involving the effect of ARBs on prevention of new-onset type 2 diabetes and cardiovascular events. Studies were included if they were randomized controlled trials versus placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. Results Eleven trials were identified, including 82738 patients. ARBs prevented new-onset type 2 diabetes （odds ratio 0.8 （95% CI 0.76, 0.85））. Regardless of indication for use, essential hypertension （seven trials）, impaired glucose tolerance （one trial）, cardiocerebrovascular disease （two trials） or heart failure （one trial）, reductions in new-onset type 2 diabetes were maintained （0.75 （0.69, 0.82）, 0.85 （0.78, 0.92）, 0.80 （0.76, 0.85） and 0.80 （0.64, 0.99）, respectively）. No statistical heterogeneity was observed for any evaluation. However, ARBs did not significantly reduce the odds of all-cause mortality, myocardial infarction and heart failure versus control therapy among all of these studies. But ARBs did reduce the odds of cardiac death and heart failure among the heart failure study versus control therapy. Conclusion ARBs have significant ability to reduce risk of developing new-onset type 2 diabetes but does not improve cardiovascular outcomes over the study follow-up periods among all of included studies.
