龙蛇九味汤联合坎地沙坦酯片对高血压患者Renin、AngⅡ与ALD的影响

目的:研究龙蛇九味汤联合坎地沙坦酯片治疗高血压的疗效及其对患者肾素(Renin)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)及醛固酮(aldosterone,ALD)水平的影响。方法:将高血压患者99例按照随机数字表法分为观察组(50例,予龙蛇九味汤联合坎地沙坦酯片治疗)和对照组(49例,予坎地沙坦酯片治疗)。比较两组治疗效果,观察两组患者治疗前后甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平。检测两组患者治疗前后血浆Renin、AngⅡ及ALD水平。结果:观察组疗效优于对照组(P<0.05);治疗后观察组TG、TC、LDL-C及血压晨峰值、收缩压、舒张压以及血浆Renin、AngⅡ、ALD均低于对照组(P<0.05),HDL-C高于对照组(P<0.05)。结论:龙蛇九味汤联合坎地沙坦酯有助于纠正高血压患者血脂紊乱情况,提高治疗效果,可能与其降低Renin、AngⅡ及ALD水平,调节肾素-血管紧张素-醛固酮系统有关。

The Beneficial Effect of Renin-Angiotensin-Aldosterone System Blockade in Treatment of Hypertension, Resistant to Conventional Antihypertensives, in Patients on Maintenance Hemodialysis

Background: Hypertension (HTN) is present in up to 90% of end stage kidney disease (ESRD) patients irrespective of the etiology of their kidney disease. Moreover, it is an important modifiable risk factor for progression to ESRD and its overall cardiovascular morbidity and mortality. Objective: to evaluate, prospectively, the role of Renin-Angiotensin-Aldosterone System blockade (RAAS) in HTN, resistant to 3 conventional antihypertensives, in patients on maintenance hemodialysis (MHD). Patients and methods: A total of 52 such patients were treated with Ramipril and 5 with Losartan after intolerable cough/shortness of breath following Ramipril-use. None of the patients had fluid depletion, renal artery stenosis and primary endocrinopathy. The study group was compared to a matched control group of MHD patients with normal blood pressure following 3 drugs-combination therapies. Results: All patients, with resistant HTN, had significant activation of RAAS system prior to treatment compared to inactive one in the control group. In those with resistant HTN, control of HTN, was established within 2 weeks of therapy and was associated with suppression of the RAAS. Such therapy was associated with minor side effects. Conclusion: Our study has shown that RAAS blockade is safe and effective in controlling such resistant HTN in MHD patients.

白大衣高血压患者血清TC、hs-crp、renin和IMT变化的临床研究

目的:探讨白大衣高血压患者颈动脉内膜中层厚度(IMT)、血清总胆固醇(TC)、血清高敏c-反应蛋白(hscrp)、血清肾素(renin)的变化及临床意义。方法:选择白大衣高血压患者75例,原发性高血压患者58例,健康查体者52例,测定三组TC、hscrp、renin水平以及IMT,对三组数据进行统计学分析。结果:白大衣高血压组和原发性高血压组相比,血清TC、hs CRP、renin水平以及IMT比较,差异无统计学意义(P>0.05);白大衣高血压组、原发性高血压组与健康查体者相比,各项指标比较,差异有统计学意义(P<0.05)。白大衣高血压组与原发性高血压组IMT厚度与TC、hs CRP、renin水平成正相关。结论:白大衣高血压和原发性高血压均存在炎性反应以及早期动脉硬化,均应引起重视。

Inhibition of renin activity by aliskiren ameliorates diabetic nephropathy in type 1 diabetes mouse model

Renin is the rate-limiting enzyme of the reninangiotensin system (RAS). In addition to its enzymatic activity to generate angiotensin I, renin also signals through the (pro)renin receptor to exert angiotensin II-independent effects. In this study we examined the effect of renin inhibition on the development of diabetic nephropathy. Male DBA/2J mice were induced to diabetes with streptozotocin, and the diabetic mice were treated for 16 weeks with saline or aliskiren, a renin enzymatic inhibitor. Aliskiren treatment had little effects on blood glucose and blood pressure in diabetic mice. Saline-treated mice developed progressive albuminuria and glome-rulosclerosis, and aliskiren treatment effectively alleviated albumiuria and glomerulosclerosis. Morphologically aliskiren treatment prevented the thickening of the glomerular basement membrane and reduced podocyte loss. At the molecular levels, aliskiren prevented the decline of slit diaphragm proteins and blocked the synthesis of extracellular matrix and pro-fibrotic factors in the diabetic kidney. Aliskiren treatment results in compensatory renin increase in the glomeruli due to blockade of the negative feedback loop, and also partially suppressed the intracellular signaling mediated by the (pro)renin receptor activated in hyperglycemia. These observations suggest that the therapeutic activity of aliskiren to prevent diabetic renal injury is contributed by inhibition of both the angiotensin II-dependent and -independent pathways. Taken together, it is concluded that inhibition of renin enzymatic activity ameliorates diabetic renal injury in type 1 diabetes, and support the use of aliskiren in diabetes kidney disease.

Possible contribution of(pro)renin receptor to development of gestational diabetes mellitus

(Pro)renin receptor [(P)RR], a receptor for renin and prorenin, was first cloned in 2002. Since then, the pathophysiological roles of(P)RR have been growing concerns.(P)RR binds renin and prorenin, with two important consequences, nonproteolytic activation of prorenin, leading to the tissue renin-angiotensin system activation and the intracellular signalings. It is now also known to play an important role as vacuolar H+-ATPase associated protein, involving in Wnt signaling, main component of embryonic development. Extracellular domain of full-length(P)RR is cleaved in golgi-complex forming soluble(P)RR [s(P)RR]. The s(P)RR is now possible to be measured in human blood and urine. It is now measured in different pathophysiological states, and recent study showed that elevated plasma s(P)RR levels in the early stage of pregnancies are associated with higher incidence of gestational diabetes mellitus later in the pregnancies. Plasma s(P)RR levels of neonates are known to be higher than that of adults. It was also shown that, increased s(P)RR concentrations in cord blood, associated with a lower small for gestational age birth likelihood. These data suggests the involvement of(P)RR in embryo's growth. In thisreview article, we attempt to figure out the possible pathophysiological roles of the(P)RR in maternal glucose intolerance and embryo's growth, through reviewing previous studies.

Renin and cardiovascular disease:Worn-out path,or new direction?

Inhibition of the renin angiotensin system has beneficial effects in cardiovascular prevention and treatment. The advent of orally active direct renin inhibitors adds a novel approach to antagonism of the renin-angiotensin system.Inhibition of the first and rate-limiting step of the renin angiotensin cascade offers theoretical advantages over downstream blockade.However,the recent discovery of the(pro)renin receptor which binds both renin and prorenin,and which can not only augment catalytic activity of both renin and prorenin in converting angiotensinogen to angiotensinⅠ,but also signal intracellularly via various pathways to modulate gene expression,adds a significant level of complexity to the field.In this review,we will examine the basic and clinical data on renin and its inhibition in the context of cardiovascular pathophysiology.

Role of the renin angiotensin system in diabetic nephropathy

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.

Renin-angiotensin system in the pathogenesis of liver fibrosis

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.

Renin angiotensin system in liver diseases: Friend or foe?

In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?synthesis.In this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two axes.The first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases.In this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal syndrome.The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

Inflammation, oxidative stress and renin angiotensin system in atherosclerosis

Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin Ⅱ(Ang Ⅱ) and a decrease in nitric oxide. The renin-angiotensin system(RAS), and its primary mediator Ang Ⅱ, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors(angiotensin-converting enzyme inhibitors)], Ang Ⅱ receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in Apo E-deficient atherosclerotic mice.

Systematic review: Renin-angiotensin system inhibitors in chemoprevention of hepatocellular carcinoma

BACKGROUND Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the antiangiogenic and anti-fibrogenic activity of these drugs. AIM To elucidate the role of ARBs and ACE-Is in HCC. METHODS We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma;moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were:(1) prospective or retrospective clinical studies;(2) epidemiological studies;and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals.RESULTS Thirty-one studies were selected. Three interventional studies showed that ACEIs had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.

Therapeutic potential of targeting the renin angiotensin system in portal hypertension

Portal hypertension is responsible for the bulk of the morbidity and mortality in patients with cirrhosis.Drug therapy to reduce portal pressure involves targeting two vascular beds.The first approach is to reduce intra hepatic vascular tone induced by the activity of powerful vasocontrictors such as angiotensin Ⅱ,endothelin-1 and the sympathetic system and mediated via contraction of perisinusoidal myofibroblasts and pervascular smooth muscle cells.The second approach is to reduce mesenteric and portal blood flow.Non-selective b-blockers are widely used and have been shown to prolong patient survival and reduce oesophageal variceal bleeding in advanced cirrhosis.However many patients are unable to tolerate these drugs and they are ineffective in a significant proportion of patients.Unfortunately there are no other drug therapies that have proven efficacy in the treatment of portal hypertension and prevention of variceal bleeding.This review briefly outlines current therapeutic approaches to themanagement of portal hypertension,and the evidence supporting the role of the renin angiotensin system(RAS) and the use of RAS blockers in this condition.It will also outline recent advances in RAS research that could lead to the development of new treatments focusing in particular on the recently discovered "alternate axis" of the RAS.

Effect of propranolol on the splanchnic and peripheral renin angiotensin system in cirrhotic patients

AIM:To evaluate the effect of β-blockade on angiotensins in the splanchnic and peripheral circulation of cirrhotic patients and also to compare hemodynamic parameters during liver transplantation according to propranolol pre-treatment or not. METHODS:Patients were allocated into two groups:outpatients with advanced liver disease(LD) and during liver transplantation(LT). Both groups were subdivided according to treatment with propranolol or not. Plasma was collected through peripheral venipuncture to determine plasma renin activity(PRA),Angiotensin(Ang) Ⅰ,Ang Ⅱ,and Ang-(1-7) levels by radioimmunoassay in LD group. During liver transplantation,hemodynamic parameters were determined and blood samples were obtained from the portal vein to measure renin angiotensin system(RAS) components.RESULTS:PRA,Ang Ⅰ,Ang Ⅱ and Ang-(1-7) were signifi cantly lower in the portal vein and periphery in all subgroups treated with propranolol as compared to non-treated. The relationships between Ang-(1-7) and Ang Ⅰ levels and between Ang Ⅱ and Ang Ⅰ were significantly increased in LD group receiving propranolol. The ratio between Ang-(1-7) and Ang Ⅱ remained unchanged in splanchnic and peripheral circulation in patients under β-blockade,whereas the relationship between Ang Ⅱ and Ang Ⅰ was significantly increased in splanchnic circulation of LT patients treated with propranolol. During liver transplantation,cardiac output and index as well systemic vascular resistance and index were reduced in propranolol-treated subgroup. CONCLUSION:In LD group,propranolol treatment reduced RAS mediators,but did not change the ratio between Ang-(1-7) and Ang Ⅱ in splanchnic and peripheral circulation. Furthermore,the modification of hemodynamic parameters in propranolol treated patients was not associated with changes in the angiotensin ratio.

Nonalcoholic fatty liver disease and the renin-angiotensin system:Implications for treatment

Nonalcoholic fatty liver disease(NAFLD) is the commonest liver disease in Western countries.Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far.Emerging evidence,mainly from animal studies,suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors(ACE-I) and angiotensin receptor blockers(ARBs) as a potentially useful therapeutic approach.However,data from human studies are limited and contradictory.In addition,there are few randomized controlled trials(RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies,pilot prospective studies and post hoc analyses of clinical trials.Accordingly,more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.

Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients

Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion.

What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?

The kallikrein-kinin system(KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors(B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system(RAS) is an important blood pressure regulator and controls both sodium and water intake. AngⅡ is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngⅡ acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

Effect of Renin Angiotensin System Blockade on the Islet Microvessel Density of Diabetic Rats and Its Relationship with Islet Function

To investigate the effects of rennin angiotensin system blockade on the microvessel density in islets of diabetic rats and its relationship with islet function, diabetes model was created by feeding of high-caloric laboratory chow plus intraperitoneal injection of a small dose of streptozotocin （30 mg/kg）. After 8 weeks intervention with perindopril （AE, n=10） or valsartan （AR, n=10）, the islet function of the animals was evaluated by intravenous insulin release test （IVIRT）. The pancreases were immunohistochemically stained to analyze the content of insulin and vascular endothelial growth factor （VEGF） in the islets. The microvessel density （MVD） of islets was detected by counting CD34 positive cells. The hypoxia inducible factor （HIF）-1α mRNA expression in the islets was detected by RT-PCR. Compared with normal control group （NC, n=10）, the area under the curve for insulin from 0 to 30 min （AUCI0-30） of diabetes group （DM, n=8） was decreased by 66.3%; the insulin relative concentration （IRC） of βcell was decreased significantly; the relative content of VEGF was increased obviously [（–4.21±0.13） vs （–4.06±0.29）]; MVD in islets was decreased by 71.4%; the relative expression of HIF-1α mRNA was increased by 1.19 times （all P〈0.01）. Compared with DM group, the AUCI0-30 of AE and AR group was increased by 44.6% and 34.9% respectively; IRC was also increased significantly; the relative content of VEGF was decreased by 21.2% and 21.7% respectively; MVD was increased by 62.5% and 75.0% respectively; the relative expression of HIF-1α was decreased by 27.2% and 29.0% respectively （all P〈0.01 or P〈0.05）. There were no significant differences in the said indexes between group AE and AR. It is concluded that the blockade of RAS may ameliorate islets function of diabetic rats by increasing the MVD in islets.

Effect of Topical Propranolol Gel on Plasma Renin,Angiotensin Ⅱ and Vascular Endothelial Growth Factor in Superficial Infantile Hemangiomas

The effect of topical propranolol gel on the levels of plasma renin,angiotensin Ⅱ（ATⅡ） and vascular endothelial growth factor（VEGF） in superficial infantile hemangiomas（IHs） was investigated. Thirty-three consecutive children with superficial IHs were observed pre-treatment,1 and 3 months after application of topical propranolol gel for the levels of plasma renin,AT Ⅱand VEGF in Department of General Surgery of Dongfang Hospital from February 2013 to February 2014. The plasma results of IHs were compared with those of 30 healthy infants of the same age from out-patient department. The clinical efficiency of topical propranolol gel at 1st,and 3rd month after application was 45%,and 82% respectively. The levels of plasma renin,AT and VEGF in patients preⅡ-treatment were higher than those in healthy infants（565.86±49.66 vs. 18.19±3.56,3.20±0.39 vs 0.30±0.03,and 362.16±27.29 vs. 85.63±8.14,P〈0.05）. The concentrations of VEGF and renin at 1st and 3rd month after treatment were decreased obviously as compared with those pre-treatment（271.51±18.59 vs. 362.16±27.29,and 405.18±42.52 vs. 565.86±49.66 P〈0.05; 240.80±19.89 vs. 362.16±27.29,and 325.90±35.78 vs. 565.86±49.66,P〈0.05,respectively）,but the levels of plasma AT declined slightly Ⅱ（2.96±0.37 vs. 3.20±0.39,and 2.47±0.27 vs. 3.20±0.39,P〉0.05）. It was indicated that the increased renin,AT Ⅱand VEGF might play a role in the onset or development of IHs. Propranolol gel may suppress the proliferation of IHs by reducing VEGF.

African Americans,hypertension and the renin angiotensin system

African Americans have exceptionally high rates of hypertension and hypertension related complications. It is commonly reported that the blood pressure lowering efficacy of renin angiotensin system(RAS) inhibitors is attenuated in African Americans due to a greater likelihood of having a low renin profile. Therefore these agents are often not recommended as initial therapy in African Americans with hypertension. However, the high prevalence of comorbid conditions, such as diabetes, cardiovascular and chronic kidney disease makes treatment with RAS inhibitors more compelling. Despite lower circulating renin levels and a less significant fall in blood pressure in response to RAS inhibitors in African Americans, numerous clinical trials support the efficacy of RAS inhibitors to improve clinical outcomes in this population, especially in those with hypertension and risk factors for cardiovascular and related diseases. Here, we discuss the rationale of RAS blockade as part of a comprehensive approach to attenuate the high rates of premature morbidity and mortality associated with hypertension among African Americans.

Pericytes synthesize renin

AIM： To investigate renin expression in pericytes dur-ing normal kidney development and after deletion of angiotensinogen, the precursor for all angiotensins.METHODS： We examined the distribution of renin ex-pressing cells by immunoshistochemistry in the intersti-tial compartment of wild type （WT） and angiotensino-gen deficient （AGT -/-） mice at different developmental stages from embryonic day 18 （E18： WT, n = 4; AGT -/-, n = 5） and at day 1 （P1： WT, n = 5; AGT -/-, n = 5）, 5 （P5： WT, n = 7; AGT -/-, n = 8）, 10 （P10： WT, n = 3; AGT -/-, n = 5）, 21 （P21： WT, n = 7; AGT -/-, n =5）, 45 （P45： WT, n = 3; AGT -/-, n = 3）, and 70 （P70： WT, n = 2; AGT -/-, n = 2） of postnatal life. We quanti-fied the number of pericytes positive for renin at all the developmental stages mentioned above and compared the results of AGT -/- mice to their WT counterparts.RESULTS： In WT mice, renal interstitial pericytes syn-thesize renin in early life supporting a lineage relation-ship with renin cells in the vasculature. The number of pericytes positive for renin per area of 0.32 mm2 （density） in WT mice was maintained from fetal life till weaning age （E18 = 4.25 ± 0.63, P1 = 3.75 ± 0.48, P5 = 3.75 ± 0.48, P10 = 4 ± 0.71, P21 = 3.8 ± 0.58） and markedly decreased in adult life （P45 = 1.2 ± 0.37, P70 = 0.8 ± 0.20）. On the other hand, in AGT -/- mice the density of pericytes expressing renin was not signifi-cantly different from WT mice at E18 and P1： E18 = 5.75 ± 0.50 vs 4.25 ± 0.63 （ P = 0.106）, P1 = 9.25 ± 3.50 vs 3.75 ± 0.48 （ P = 0.175） but significantly increased from P5 till P70： P5 = 38.25 ± 5 vs 3.75 ± 0.48 （ P = 0.0004）, P10 = 173 ± 7.50 vs 4 ± 0.70 （ P = 5.24567 × 10^-7）, P21 = 83 ± 6.70 vs 3.8 ± 0.58 （P = 2.97358 × 10^-6）, P45 = 49 ± 3.50 vs 1.2 ± 0.37 （P = 8.18274 × 10^-7） and P70 = 17.8 ± 2.30 vs 0.8 ± 0.20 （ P = 3.51151 × 10^-5）. The AGT -/- mice showed a marked increase in the number of pericytes per field studied starting from P5, reaching its peak at P10, and then a gradually de-creasing until P70.CONCLUSION： Interstitial pericytes synthesize renin during development and the number of renin-express-ing pericytes increases in response to a homeostatic threat imposed early in life such as lack of angioten-sinogen.