Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficia...Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the N^(G)-nitro-L-arginine methyl ester(L-NAME)treated rat,as well as to compare the differential effects of fasudil and angiotensin Ⅱ receptor antagonist valsartan on vascular function.In the present study,both valsartan and fasudil exerted antihypertensive action on the L-NAME-treated rats,while only va lsartan attenuated the cardiac hypertrophy.Treatment with valsartan showed improvement on vascular reactivity to norepinephrine,KCl and CaCl_(2),whereas fasudil therapy showed little effect on vasoconstriction.Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy.The increased expression of RhoA and Rho-kinase(ROCK)in the vasculature was corrected well to normal level by either valsartan or fasudil administration,which seemed to be at least partially responsi ble for the beneficial effect of the drug infusion.These findings suggest that the angiotensin Ⅱ receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor,whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin Ⅱ receptor.展开更多
Background：Mineral and bone disorder （MBD）,especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease （CKD）.However,CKD-MBD among Chinese population...Background：Mineral and bone disorder （MBD）,especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease （CKD）.However,CKD-MBD among Chinese population was poorly studied.This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD.Methods：Chinese Cohort Study of Chronic Kidney Disease （C-STRIDE） is a prospective multicenter cohort study involving predialysis CKD patients in China.Markers of MBD,including serum phosphorus,calcium,and intact parathyroid hormone,were measured in baseline samples at the patients＆#39; entry.The association between serum phosphorus and abdominal aortic calcification （AAC）,left ventricular hypertrophy （LVH） were examined by logistic regression models.Results：Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min^- 1· 1.73 m^- 2 were included.The proportion of patients with hyperphosphatemia were 2.6%,2.9%,6.8%,and 27.1% in CKD Stages 3a,3b,4,and 5,respectively.Moreover,71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder （PB）.Lateral abdominal X-rays were obtained in 2280 patients,9.8% of the patients were diagnosed as having AAC.Altogether 2219 patients had data of echocardiography,and 13.2% of them were diagnosed with LVH.Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH.Conclusions：In Chinese patients with CKD,the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal.The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.展开更多
目的探讨肌微管素相关微蛋白7(myotubularin related protein 7,MTMR7)在肺动脉高压中的作用及机制。方法健康♂小鼠、Mtmr7转基因(Mtmr7-Tg)小鼠各20只,分为对照组、Mtmr7-Tg组、野百合碱(monocrotaline,MCT)组、MCT+Mtmr7-Tg组,超声...目的探讨肌微管素相关微蛋白7(myotubularin related protein 7,MTMR7)在肺动脉高压中的作用及机制。方法健康♂小鼠、Mtmr7转基因(Mtmr7-Tg)小鼠各20只,分为对照组、Mtmr7-Tg组、野百合碱(monocrotaline,MCT)组、MCT+Mtmr7-Tg组,超声测量肺动脉血流加速时间(pulmonary artery acceleration time,PAT)和射血时间(pulmonary artery ejection time,PET),取材时分离右心室游离壁,计算右心肥厚指数,免疫染色观察肺小动脉重构。将小鼠肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)以低氧处理,观察其增殖和迁移情况。结果MTMR7在肺血管中表达,并且MCT处理之后,Mtmr7-Tg小鼠的PAT/PET比值降低(P<0.05),右心肥厚指数升高(P<0.01)。以Mtmr7基因过表达腺病毒转染PASMCs,可以抑制其增殖和迁移。用chemerin-9恢复p-ERK1/2的活性,过表达MTMR7对PASMCs增殖、迁移抑制作用消失。结论过表达MTMR7可减轻低氧诱导的小鼠PASMCs增殖和迁移,从而逆转肺动脉高压,机制与MTMR7降低ERK1/2磷酸化密切相关。展开更多
基金This study was supported by the National Natural Science Foundation of China(No.30572182)National Scientific&Technological Major Special Project-“Significant Creation of New Drugs”(Nos.2009ZX09302-003 and 2009ZX09501-021).
文摘Little attention has been paid to the effect of Rho-kinase inhibitor on the vascular dysfunction of nitric oxide-deficient hypertension.We aimed to investigate whether the Rho-kinase inhibitor fasudil showed beneficial effect on the vascular dysfunction of the N^(G)-nitro-L-arginine methyl ester(L-NAME)treated rat,as well as to compare the differential effects of fasudil and angiotensin Ⅱ receptor antagonist valsartan on vascular function.In the present study,both valsartan and fasudil exerted antihypertensive action on the L-NAME-treated rats,while only va lsartan attenuated the cardiac hypertrophy.Treatment with valsartan showed improvement on vascular reactivity to norepinephrine,KCl and CaCl_(2),whereas fasudil therapy showed little effect on vasoconstriction.Endothelium-dependent vasodilation to acetylcholine was reduced in the NO-deficient group but was normalized by the fasudil therapy.The increased expression of RhoA and Rho-kinase(ROCK)in the vasculature was corrected well to normal level by either valsartan or fasudil administration,which seemed to be at least partially responsi ble for the beneficial effect of the drug infusion.These findings suggest that the angiotensin Ⅱ receptor antagonist interferes more with the contractile response than Rho-kinase inhibitor,whereas inhibition of Rho-kinase activity exhibits a better improvement on vasorelaxation than blockade of angiotensin Ⅱ receptor.
文摘Background：Mineral and bone disorder （MBD）,especially hyperphosphatemia,is an independently risk factor for adverse prognosis in patients with chronic kidney disease （CKD）.However,CKD-MBD among Chinese population was poorly studied.This study aimed to investigate the status of MBD and its association with cardiovascular parameters in Chinese patients with predialysis CKD.Methods：Chinese Cohort Study of Chronic Kidney Disease （C-STRIDE） is a prospective multicenter cohort study involving predialysis CKD patients in China.Markers of MBD,including serum phosphorus,calcium,and intact parathyroid hormone,were measured in baseline samples at the patients＆#39; entry.The association between serum phosphorus and abdominal aortic calcification （AAC）,left ventricular hypertrophy （LVH） were examined by logistic regression models.Results：Altogether 3194 predialysis patients with mean estimated glomerular filtration of 51.8 ± 33.1 ml·min^- 1· 1.73 m^- 2 were included.The proportion of patients with hyperphosphatemia were 2.6%,2.9%,6.8%,and 27.1% in CKD Stages 3a,3b,4,and 5,respectively.Moreover,71.6% of the patients with hyperphosphatemia did not receive any phosphate-binder （PB）.Lateral abdominal X-rays were obtained in 2280 patients,9.8% of the patients were diagnosed as having AAC.Altogether 2219 patients had data of echocardiography,and 13.2% of them were diagnosed with LVH.Multivariate logistic regression analysis showed that serum phosphorus was independently associated with the presence of AAC and LVH.Conclusions：In Chinese patients with CKD,the percentage of hyperphosphatemia is comparable to that of other countries while the usage of PBs is suboptimal.The prevalence of vascular calcification in Chinese patients is relatively lower compared with the Caucasian population.
