对130例高血压病患者及70名健康人的肾素(PRA)、血管紧张素Ⅱ(ATⅡ)、醛固酮及血浆心钠素(ANP)水平的检测及对其与中医辨证分型关系进行探讨。结果表明:(1)高血压患者基础 PRA 值低于健康人,而各型组间差异较大;阳亢型组 PRA、ATⅡ明显...对130例高血压病患者及70名健康人的肾素(PRA)、血管紧张素Ⅱ(ATⅡ)、醛固酮及血浆心钠素(ANP)水平的检测及对其与中医辨证分型关系进行探讨。结果表明:(1)高血压患者基础 PRA 值低于健康人,而各型组间差异较大;阳亢型组 PRA、ATⅡ明显高于对照组和阴虚阳亢、阴阳两虚组,组间差异非常显著(P<0.01～0.001)。说明PRA 及 ATⅡ在高血压中医分型中,可以作为区别各证型不同病理生理变化的客观指标之一。(2)高血压病患者 ANP 明显低于健康人(P<0.01),但三个中医证型组间无差异(P>0.05)。(3)对高血压患者严重心脑并发症的发生与中医证型及 PRA 水平的关系,各证型间转化与 PRA 水平关系作了初步探讨。展开更多
Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of ...Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.展开更多
Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result i...Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.展开更多
Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance a...Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pat展开更多
Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress ...Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI) Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery The experiment protocol included shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&T) combination of the two At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) in the surviving septum myocardium, and survival rates were calculated Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<展开更多
Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is consid...Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.展开更多
Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinve...Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinvestigated on other diseases, such as infections, can-cer and cardiovascular diseases. Recently, both the dis-covery of paracrine actions of vitamin D(recognized as"local vitamin D system") and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its ac-tive cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between obser-vational and interventional studies emphasize the frag-mentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.展开更多
文摘对130例高血压病患者及70名健康人的肾素(PRA)、血管紧张素Ⅱ(ATⅡ)、醛固酮及血浆心钠素(ANP)水平的检测及对其与中医辨证分型关系进行探讨。结果表明:(1)高血压患者基础 PRA 值低于健康人,而各型组间差异较大;阳亢型组 PRA、ATⅡ明显高于对照组和阴虚阳亢、阴阳两虚组,组间差异非常显著(P<0.01～0.001)。说明PRA 及 ATⅡ在高血压中医分型中,可以作为区别各证型不同病理生理变化的客观指标之一。(2)高血压病患者 ANP 明显低于健康人(P<0.01),但三个中医证型组间无差异(P>0.05)。(3)对高血压患者严重心脑并发症的发生与中医证型及 PRA 水平的关系,各证型间转化与 PRA 水平关系作了初步探讨。
文摘Hepatic fibrosis is considered a common response to many chronic hepatic injuries. It is a multifunctional process that involves several cell types, cytokines, chemokines and growth factors leading to a disruption of homeostatic mechanisms that maintain the liver ecosystem. In spite of many studies regarding the development of fibrosis, the understanding of the pathogenesis remains obscure. The hepatic tissue remodeling process is highly complex, resulting from the balance between collagen degradation and synthesis. Among the many mediators that take part in this process, the components of the Renin angiotensin system （RAS） have progressively assumed an important role. Angiotensin （Ang） II acts as a profibrotic mediator and Ang-（1-7）, the newly recognized RAS component, appears to exert a counter-regulatory role in liver tissue. We briefly review the liver fibrosis process and current aspects of the RAS. This review also aims to discuss some experimental evidence regarding the participation of RAS mediators in the pathogenesis of liver fibrosis, focusing on the putative role of the ACE2-Ang-（1-7）- Mas receptor axis.
文摘Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.
基金Supported by National Health and Medical Research Council (NHMRC) of Australia Project Grants,No. APP1124125。
文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pat
文摘Background Congestive heart failure (CHF) is a major cause of morbidity and mortality worldwide and angiotensin convertingenzyme inhibitor (ACEI) is the cornerstone in its treatment However, CHF continues to progress despite this therapy, perhaps because of production of angiotensin Ⅱ (Ang Ⅱ) by alternative pathways The present study was conducted to examine the combined effects of a chronic ACEI, ramipril, and a chronic Ang Ⅱ type 1 receptor blocker, TCV116, on rat CHF after myocardial infarction (MI) Methods Congestive heart failure was caused by MI in rats, which was induced by ligating the left anterior descending coronary artery The experiment protocol included shamoperated rats (Sham), MIcontrol rats (MIcontrol), MI rats treated with ramipril 3 mg/kg (MIramipril) or TCV116 2 mg/kg (MITCV116) per day, half dosage (MI1/2R&T) or full dosage (MIR&T) combination of the two At 22 weeks, cardiac hemodynamic parameters such as mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), maximal rate of left ventricule pressure development and decline (LV dP/dtmax) and left ventricular end diastolic pressure (LVEDP), and cardiac morphometric parameters such as heart weight (HW), left ventricular weight (LVW) and left ventricular cavity area (LVCA) were measured, mRNA expressions of cardiac molecule genes such as β myosin heavy chain (βMHC), Btype natriuretic peptide (BNP), transforming growth factorβ1 (TGFβ1), collagen I and Ⅲ were quantified with reverse transcription polymerase chain reaction (RTPCR) in the surviving septum myocardium, and survival rates were calculated Results There were no significant differences in MI sizes (%) among each MI related experimental groups (33±13, 34±14, 33±13, 35±13 and 33±14 for MIcontrol, MIramipril, MITCV116, MI1/2R&T and MIR&T, respectively, no statistical significance for all) Compared with shamoperated rats, MI rats without therapy showed significant increases in morphometric parameters as well as in mRNA expressions of cardiac molecule genes (P<
基金Supported by The Toho University School of Medicine Research Foundation
文摘Renin angiotensin system （RAS） activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme （ACE）-angio-tensin Ⅱ （Ang Ⅱ）-Ang Ⅱ type 1 （AT1） axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang Ⅱ are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang Ⅰ and the catabolism of Ang Ⅱ to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang Ⅱ-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2.
基金Supported by European Commission(FP7-INNOVATION I HEALTH-F2-2013-602114Athero-B-Cell:Targeting and exploiting B cell function for treatment in cardiovascular disease)to Dr.F Mach+3 种基金Swiss National Science Foundation Grants to Dr.F Mach,No.#310030_118245Swiss National Science Foundation Grants to Dr.N Vuilleumier,No.#310030_140736and Swiss National Science Foundation Grants to Dr.F Montecucco,No.#32003B_134963/1the Novartis Foundation and the Foundation"Gustave and Simone Prévot"to Dr.F Montecucco
文摘Vitamin D deficiency has been indicated as a pandemicemerging public health problem. In addition to the well-known role on calcium-phosphorus homeostasis in thebone, vitamin D-mediated processes have been recentlyinvestigated on other diseases, such as infections, can-cer and cardiovascular diseases. Recently, both the dis-covery of paracrine actions of vitamin D(recognized as"local vitamin D system") and the link of vitamin D with renin-angiotensin-aldosterone system and the fibroblast growth factor 23/klotho pathways highlighted its ac-tive cardiovascular activity. Focusing on hypertension, this review summarizes the more recent experimental evidence involving the vitamin D system and deficiency in the cardiovascular pathophysiology. In particular, we updated the vascular synthesis/catabolism of vitamin D and its complex interactions between the various endocrine networks involved in the regulation of blood pressure in humans. On the other hand, the conflicting results emerged from the comparison between obser-vational and interventional studies emphasize the frag-mentary nature of our knowledge in the field of vitamin D and hypertension, strongly suggesting the need of further researches in this field.
