目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和...目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和对离子通道的作用。(2)使用过表达电压门控性钾(voltage-gated potassium channel,Kv)通道2.1亚型(Kv2.1)的慢病毒转染中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞构建CHO-Kv2.1细胞系,使用膜片钳技术观察替米沙坦对Kv2.1通道的直接作用。结果缬沙坦和厄贝沙坦无类似替米沙坦的高糖浓度下促胰岛素分泌、升高β细胞内Ca^(2+)浓度和抑制β细胞的Kv通道等作用。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)阻断剂GW9662亦未阻断替米沙坦的上述作用。而替米沙坦可以浓度依赖性地抑制CHO-Kv2.1细胞的Kv2.1通道电流。结论替米沙坦的促胰岛素分泌作用可能与血管紧张素Ⅱ-1型(angiotensin II type 1,AT-1)受体和PPARγ无关,但至少与对Kv2.1通道的直接抑制作用有关。展开更多
Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents ...Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.展开更多
The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization...The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.展开更多
A rapid and sensitive liquid chromatography-tandem mass spectrometric （LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma....A rapid and sensitive liquid chromatography-tandem mass spectrometric （LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma. Carbamazepine was used as an internal standard. Analytes and the internal standard were extracted from human plasma by solid-phase extraction technique using Waters Oasis HLB 1 cm3 （30 mg） extraction cartridge. The reconstituted samples were chromatographed on a Hypurity advance C18 column （50mm × 4.6mm, 5 gm） using a mixture of acetonitrile -5 mM ammonium acetate buffer （pH-4.0） （50：50, v/v） as the mobile phase at a flow rate of 0.8mL/min. The calibration curve obtained was linear （r_〉0.99） over the concentration range of 2.01-400.06 ng/mL for telmisartan and 0.05 -10.01 ng/mL for amlodipine. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The proposed method was found to be applicable to clinical studies.展开更多
Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the sup...Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ （PPARγ） has been proposed to decrease the effects of transforming growth factor-β （TGF-β） on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type 1 receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced glomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element （PPRE） was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type 1 receptor blocker, up-regulated PPARγ protein levels in a dose-dependent manner （P〈0.05）. Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner （P〈0.05）. Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ, blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.展开更多
We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel-...We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel- misartan group （n = 9） and the high-fat diet group （n = 10）. The control group consisted of age-matched rats on a regular diet （n = 10）. At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisar- tan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension.展开更多
This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups...This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random：ND group（n=10） and HD group（n=10）,in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation;ND＋telmisartan（n=10） group and HD＋telmisartan group（n=10）,in which the rats were initially administered in the same way as the ND or HD group,and then they were orally gavaged with telmisartan（5 mg/kg daily） additionally for 5 weeks.Related inflammatory factors were measured by ELISA.Monocyte chemotactic protein 1（MCP-1）,phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting.CRP and angiotensin Ⅱ receptor 1（AT1） mRNA expressions in both adipose and liver were determined by RT-PCR.The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels,plasma fasting insulin levels and homeostasis model of assessment-insulin resistance（HOMA-IR）.Furthermore,telmisartan administration significantly reduced serum CRP,TNF-α and IL-1β levels,and elevated serum IL-10 levels.It was also found to hamper the high-fat diet-induced increase in CRP mRNA,AT1 mRNA and MCP-1,and decrease in IκB-α in both adipose and liver.It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways.展开更多
The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis ...The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.展开更多
文摘目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和对离子通道的作用。(2)使用过表达电压门控性钾(voltage-gated potassium channel,Kv)通道2.1亚型(Kv2.1)的慢病毒转染中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞构建CHO-Kv2.1细胞系,使用膜片钳技术观察替米沙坦对Kv2.1通道的直接作用。结果缬沙坦和厄贝沙坦无类似替米沙坦的高糖浓度下促胰岛素分泌、升高β细胞内Ca^(2+)浓度和抑制β细胞的Kv通道等作用。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)阻断剂GW9662亦未阻断替米沙坦的上述作用。而替米沙坦可以浓度依赖性地抑制CHO-Kv2.1细胞的Kv2.1通道电流。结论替米沙坦的促胰岛素分泌作用可能与血管紧张素Ⅱ-1型(angiotensin II type 1,AT-1)受体和PPARγ无关,但至少与对Kv2.1通道的直接抑制作用有关。
基金supported by grants from the Serbian Ministry for Education, Science and Technology Development (Grant No.III41026 and 175053)
文摘Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.
基金supported by grants from the National Natural Science Foundation of China(No.81270239)the Natural Science Foundation of Hubei Province of China(No.2014CFB200)
文摘The aim of this study was to investigate the possible beneficial role of telmisartan in cerebral edema after traumatic brain injury（TBI） and the potential mechanisms related to the nucleotide-binding oligomerization domain（NOD）-like receptor（NLR） pyrin domain-containing 3（NLRP3） inflammasome activation. TBI model was established by cold-induced brain injury. Male C57BL/6 mice were randomly assigned into 3, 6, 12, 24, 48 and 72 h survival groups to investigate cerebral edema development with time and received 0, 5, 10, 20 and 40 mg/kg telmisartan by oral gavage, 1 h prior to TBI to determine the efficient anti-edemic dose. The therapeutic window was identified by post-treating 30 min, 1 h, 2 h and 4 h after TBI. Blood-brain barrier（BBB） integrity, the neurological function and histological injury were assessed, at the same time, the m RNA and protein expression levels of NLRP3 inflammasome, IL-1β and IL-18 concentrations in peri-contused brain tissue were measured 24 h post TBI. The results showed that the traumatic cerebral edema occurred from 6 h, reached the peak at 24 h and recovered to the baseline 72 h after TBI. A single oral dose of 5, 10 and 20 mg/kg telmisartan could reduce cerebral edema. Post-treatment up to 2 h effectively limited the edema development. Furthermore, prophylactic administration of telmisartan markedly inhibited BBB impairment, NLRP3, apoptotic speck-containing protein（ASC） and Caspase-1 activation, as well as IL-1β and IL-18 maturation, subsequently improved the neurological outcomes. In conclusion, telmisartan can reduce traumatic cerebral edema by inhibiting the NLRP3 inflammasome-regulated IL-1β and IL-18 accumulation.
文摘A rapid and sensitive liquid chromatography-tandem mass spectrometric （LC-MS/MS） assay method has been developed and fully validated for the simultaneous quantification of telmisartan and amlodipine in human plasma. Carbamazepine was used as an internal standard. Analytes and the internal standard were extracted from human plasma by solid-phase extraction technique using Waters Oasis HLB 1 cm3 （30 mg） extraction cartridge. The reconstituted samples were chromatographed on a Hypurity advance C18 column （50mm × 4.6mm, 5 gm） using a mixture of acetonitrile -5 mM ammonium acetate buffer （pH-4.0） （50：50, v/v） as the mobile phase at a flow rate of 0.8mL/min. The calibration curve obtained was linear （r_〉0.99） over the concentration range of 2.01-400.06 ng/mL for telmisartan and 0.05 -10.01 ng/mL for amlodipine. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. A run time of 2.5 min for each sample made it possible to analyze more than 400 human plasma samples per day. The proposed method was found to be applicable to clinical studies.
基金grants from National Natural Sciences Foundation of China (No. 30672227 30571950+4 种基金 30600667 30700895 30628029 30770913) the "973" Program of China (No. 2002 CB513100)
文摘Glomerulosclerosis, defined as phenotype transition of mesangial cell and deposition of extracelluar matrix, remains a chronic disease with excessive morbidity and mortality. The molecular mechanism underlying the suppression of mesangial cell activation is not fully understood. Since activation of peroxisome proliferators-activated receptor γ （PPARγ） has been proposed to decrease the effects of transforming growth factor-β （TGF-β） on glomerulosclerosis, we examined here whether and how telmisartan, an angiotensin Ⅱ type 1 receptor blocker with PPARγ-modulating activity, inhibited TGF-β-induced glomerulosclerosis in rat glomerular mesangial cells. Protein levels of PPARγ were detected by Western blot. Activation of PPARγ response element （PPRE） was analyzed by luciferase assays. Deposition of extracelluar matrix was tested by confocol laser scanning. The results showed that telmisartan, but not valsartan, another angiotensin Ⅱ type 1 receptor blocker, up-regulated PPARγ protein levels in a dose-dependent manner （P〈0.05）. Activation of PPRE, represented by luciferase activity, was also increased with higher concentration of telmisartan in a dose-dependent manner （P〈0.05）. Furthermore, telmisartan inhibited TGF-β-induced α-smooth muscle actin expression and collagen IV secretion in mesangial cells. GW9662, an inhibitor of PPAR-γ, blocked the inhibitory effects of telmisartan on TGF-β-induced glomerulosclerosis in mesangial cells. Our study indicates a benefit of telmisartan as a PPARγ agonist against TGF-β-induced mesangial cells activation in renal glomerulus. It may provide possibility that telmisartan works as a potential agent against diabetic nephropathy and hypertensive renal disease.
基金supported by the Natural Science Foundation of China(No.30871042)
文摘We sought to investigate the effects of telmisartan on high-fat diet-induced hypertension and to explore the possible underlying mechanisms. Rats receiving high-fat diet were randomly divided into two groups, the tel- misartan group （n = 9） and the high-fat diet group （n = 10）. The control group consisted of age-matched rats on a regular diet （n = 10）. At the end of the treatment, the body weight, blood pressure, insulin sensitivity and serum adiponectin levels of all rats were examined, and their visceral fat was extracted and weighed. Our results showed that telmisartan improved insulin resistance and dyslipidemia and increased serum adiponectin levels. Telmisar- tan also lowered both systolic blood pressure and diastolic blood pressure, and decreased the accumulation of perirenal fat associated with high-fat diet. Furthermore, telmisartan increased adiponectin mRNA expression in the perirenal fat. Correlation analysis showed that both systolic blood pressure and diastolic blood pressure were positively correlated with perirenal fat. These effects of telmisartan may be mediated through decreases in perirenal fat and contributed to the improvement of perirenal fat function. Our findings suggested a strong link between perirenal fat and high-fat diet-induced hypertension, and identified telmisartan as a potential drug for the treatment of obesity-related hypertension.
基金supported by a grant from National Natural Sciences Foundation of China (No. 30971247)
文摘This study investigated the effects of telmisartan on insulin resistance in high-fat diet-treated rats and the possible mechanism.A total of 40 male Sprague-Dawley rats enrolled in the study were divided into 4 groups at random：ND group（n=10） and HD group（n=10）,in which the rats were given a normal chow diet or a high-fat diet for 20 weeks following a one-week adaptation;ND＋telmisartan（n=10） group and HD＋telmisartan group（n=10）,in which the rats were initially administered in the same way as the ND or HD group,and then they were orally gavaged with telmisartan（5 mg/kg daily） additionally for 5 weeks.Related inflammatory factors were measured by ELISA.Monocyte chemotactic protein 1（MCP-1）,phosphorylated JNK and IκB-α expressions in both adipose and liver were detected by Western blotting.CRP and angiotensin Ⅱ receptor 1（AT1） mRNA expressions in both adipose and liver were determined by RT-PCR.The results showed that telmisartan administration in vivo reversed insulin resistance as evidenced by a decrease in plasma fasting glucose levels,plasma fasting insulin levels and homeostasis model of assessment-insulin resistance（HOMA-IR）.Furthermore,telmisartan administration significantly reduced serum CRP,TNF-α and IL-1β levels,and elevated serum IL-10 levels.It was also found to hamper the high-fat diet-induced increase in CRP mRNA,AT1 mRNA and MCP-1,and decrease in IκB-α in both adipose and liver.It was concluded that telmisartan administration in vivo may improve insulin resistance through attenuated inflammatory response pathways.
基金the General Financial Grant from the China Postdoctoral Science Foundation(No.2014M560722)the Natural Science Foundation of Sichuan University of Science and Engineering(No.2015RC30)the Science and Technology Support Program of Sichuan Province of China(No.2017RZ0083).
文摘The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.
