Gene expression profiles in the peri-infarct brain cortex in a rat model of stroke-prone renovascular hypertension

BACKGROUND： Previous studies have focused on gene expression acutely following stroke onset. However, there have been a few reports of gene expression during later stages of cerebral infarction. OBJECTIVE： To determine gene expression profiling in the peri-infarct brain cortex 7 days after ischemia in a rat model of cerebral infarction in renovascular hypertensive rats. DESIGN, TIME AND SETTING： An in vivo, molecular experiment was performed at the Experimental Animal Center of Sun Yat-sen University and CapitalBio, Beijing, China between February 2004 and August 2005. MATERIALS： A 70-mer oligo chip containing 5 705 rat genes was supplied by CapitalBio, Beijing, China; and the Oligo rat gene bank was provided by Qiagen, the Netherlands. METHODS： Six Sprague Dawiey rats were utilized to establish a stroke-prone renovascular hypertensive model using the two-kidney and two-clip method. The rats were subsequently randomly assigned to two groups： middle cerebral artery occlusion and sham-operation, with three rats in each group. The middle cerebral artery occlusion model was induced by intraluminal suture method. Incisions were sutured following isolation of carotid arteries in the sham-operation group. MAIN OUTCOME MEASURES： Total RNA was extracted from the peri-infarct cerebral cortex 7 days after surgery. Following fluorescent labeling, RNA was hybridized to an Oligo chip containing 5 705 genes and was then scanned. Images were collected and the differentially expressed genes （number and category） were selected by data analysis. RESULTS： A total of 174 genes were upregulated, and 23 were downregulated, in the peri-infarct cerebral cortex 7 days after ischemia. The upregulated genes were distributed among 12 functional categories, and the downregulated genes belonged to categories of transport, transcription regulators, signals, response to stress, metabolism, and cell adhesion. The expression of some cytoskeletal genes was upregulated, including VIM, A2M, B2M, ACTR3, and ARPClB. Expression of a few cell adhesion-related genes （such as NLGN1, LGALS1, LGALS3, COLIA1, COL2A1, and SPP1） and other inflammation-related genes （such as CIQB, ClS, C4, C5R1, CFH, CD14, CD164, CD47, CD48, CD53, CD8B, IFNGR, and TFITM2） were upregulated. The glutamate-receptor gene GRIK5 was downregulated, which is related to the excitatory neurotransmitter glutamate. However, expression of the inhibitory neurotransmitter GABA-related genes was bidirectional - namely, GABRA5 downregulation and GABARAP upregulation. CONCLUSION： Upregulation of many cell adhesion and inflammation related genes and downregulation of excitatory glutamate-related receptor genes revealed active gene expression during later stages of cerebral infarction, which suggested molecular mechanisms of injury or repair.

It’s Time for New Insights into Renovascular Hypertension at the Molecular Level

At the cellular level, reduced kidney perfusion in atherosclerotic renal arthery disease (ARVD), induces hypoxia, activation of the renin-angiotensin-aldosterone system (RAAS) and cytokine activation. Impaired blood flow in the kidneys creates a microenvironment triggering significant cytokine production, contributing to vascular damage and endothelial disfunction. Interactions between cytokines and endothelial, glomerular, and tubular cells often result in increased vessel permeability, and fibrosis, and contribute to the development of chronic kidney disease (CKD). Molecules such as endothelins, prostaglandins, and nitric oxide play a crucial role at the molecular level. The imbalance between vasoconstrictor and vasodilator factors contributes to vascular dysfunction. Oxidative stress and inflammatory processes at the cellular level contribute to endothelial damage and structural changes in blood vessels. Mineralocorticoid receptor antagonists (MRAs) therapy in the context of ARVD holds promise in reducing fibrosis, promoting angiogenesis and enhancing overall outcomes in patients with this pathology. Recent data also indicates the antioxidative, anti-inflammatory, and antifibrotic effects of SGLT2 inhibitors. They reduce oxidative stress caused by hypoxic conditions and enhance renal perfusion, contributing to the preservation of cellular function. Studies employing Blood Oxygen Level-Dependent (BOLD) imaging have identified adaptations to reduced blood flow, volume, and glomerular filtration rate in post-stenotic kidneys that preserve oxygenation in the medulla and cortex during medical therapy. Data from the literature indicate that despite the partial recovery of renal hypoxia and restoration of blood flow after revascularization, inflammatory cytokines and injury biomarkers remain elevated, and the glomerular filtration rate (GFR) does not recover in ARVD. Restoration of vascular patency alone has failed to reverse tubulointerstitial damage and partially explains the limited clinical benefit of renal stenting. Considering these findings, BOLD MR imaging emerges as a technique capable of providing insights into the critical juncture of irreversibility in ARVD. However, further research is needed to monitor renal hypoxia following renal artery stenting and the inflammatory response over an extended period in conjunction with optimal therapy involving MRAs and SGLT2 agonists. The aim of research at the molecular level enables the identification of potential therapeutic modalities targeting specific molecular pathways, opening the door to innovative approaches in treating renovascular hypertension.

Expression of neurocan mRNA and ultrastructure of brain tissue after cerebral ischemia and reperfusion in stroke-prone renovascular hypertensive rats treated by electroacupuncture

We established a stroke-prone renovascular hypertensive rat model by bilateral constriction of the renal artery with sliver loop clips. After ten weeks, middle cerebral artery occlusion was induced for 2 hours. The rats then received electro-acupuncture at Baihui （DU 20） and Dazhui （DU 14） after onset of ischemia for 30 days. In situ hybridization study showed that electroacupuncture significantly reduced the number of neurocan mRNA-positive cells in the ischemic penumbra and hippocampal tissues of rats. Electron microscopy results demonstrated that the structure of neurons and blood vessels in the ischemic tissues were restored with electroacupuncture. Overall, these data suggest that electroacupuncture may protect neurons against ischemic reperfusion injury in stroke-prone renovascular hypertensive rats, which may be regulated by downregulation of expression of nerve inhibitory factor neurocan mRNA.

Protective Effects of Nobiletin on Hypertension and Cerebral Thrombosis in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

Some citrus flavonoids have been reported to possess antioxidant activities that moderate endothelial dysfunction and show protective effects on cardiovascular disease. We have investigated the protective effects of nobiletin (5,6,7,8,3’,4’-hexamethoxy flavone) derived from the peel of Citrus depressa Hayata (Shiikuwasha), a citrus fruit produced in Okinawa prefecture in Japan on hypertension and thrombogenicity in cerebral vessels of stroke-prone spontaneously hypertensive rats (SHRSP). Nobiletin was added to the diet of male SHRSP (7 weeks old) for 4 weeks. The age-related increase in systolic blood pressure usually observed in SHRSP was significantly suppressed in the treated animals. Thrombogenesis in pial blood vessels, determined using a He-Ne laser technique, and antioxidant activity, assessed by measuring urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG), were significantly reduced after treatment. Urinary nitric oxide (NO) metabolites and acetylcholine-induced endothelial relaxation were increased after dietary intervention. These results strongly suggested that antihypertensive and antithrombotic effects of nobiletin may be related to an increase in bioavailable NO, possibly mediated by the scavenging of reactive oxygen species (ROS).

Accessory renal arteries-a source of hypertension:A case report

BACKGROUND Secondary hypertension is a relatively rare condition most commonly caused by renovascular disease due to atherosclerotic vascular disease or fibromuscular dysplasia.Although accessory renal arteries are frequent,to date,only six cases of secondary hypertension determined by their existence have been reported.CASE SUMMARY We describe a case of a 39-year-old female who came to the emergency department with an urgent hypertensive crisis and hypertensive encephalopathy.Despite normal renal arteries,the computed tomography angiography revealed an inferior polar artery with 50%stenosis of its diameter.Conservative treatment with amlodipine,indapamide and perindopril was adopted,leading to blood pressure control within one month.CONCLUSION To the best of our knowledge,there are controversies regarding accessory renal arteries as a potential etiology for secondary hypertension,but the seven similar cases already described,along with the current case,could reinforce the necessity of more studies concerning this subject.

Effect of 2-Selenium Bridged β-Cyclodextrin,Glutathione Peroxidase Mimic on Stroke of Stroke-prone Spontaneously Hypertensive Rats

To investigate the treatment effect of 2-selenium bridged β -cyclodextrin(2-SeCD),a GPX mimic,on the stroke of stroke-prone spontaneously hypertensive rats(SHRSP),fifty-two SHRSP of 8-week old were randomly divided into four groups A,B,C and control group D. The rats of groups A,B,C and D were given 1.0%-1.5% NaCl mass fraction as drinking fluid. After onset of stroke,groups A,B and C were given \{orally\} 16.05,160.5 and 1605 mg·kg -1 ·day -1 of 2-SeCD,respectively,and group D was given water for \{2 weeks.\} The clinical score of stroke,systolic blood pressure(SBP),survival time of rats were recorded and the histopathologic examinations of their brain and carotid artery were made after decapitation. The clinical scores of stroke after treatment with 160.5 mg·kg -1 ·day -1 (Group B) and 1605 mg·kg -1 ·day -1 (Group C) of 2-SeCD are 2.55±0.98 and 1.98±0.79,respectively,those are obviously lower than that of group D(3.41±0.83,p<0.01). The survival days in group B(10.0±8.6) and group C(14.4±7.9) are longer than that for group D(4.7±2.9,p<0.01). The electron microscope study showed that the endothelium of carotid artery was near to normal in group B and group C,while it was seriously injured in control group D and mildly injured in group A. 2-SeCD may effectively be used to treat the stroke for SHRSP.

POTENT HYPOTENSIVE EFFECTS OF ORPHANIN FQ IN CONSCIOUS STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.

Renovascular hypertension causes cerebral vascular remodeling

Renovascular hypertensive rats （RHRs） were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

EVALUATION OF CAPTOPRIL RENOGRAPHY WITH^（99m）Tc－MAG_3 IN THE DIAGNOSIS OF RENOVASCULAR HYPERTENSION

Eighty-one patients with suspected renovascular hypertension (RVH) were studied using 99m Tc-MAG3 renography before and after administration of 25 mg captopril (CAP). Among the 81 cases, 22 were proven by renal arteriography or DSA. The results showed that by using CAP, the sensitivity and specificity of renography in RVH diagnosis increased from 66% to 72% and from 33% to 100%, respectively. We conclude that renography is a simple, noninvasive . sensitive and specific method for screening RVH and is suitable for use in hospitals with no Y-cameras.

Dietary <i>γ</i>-Aminobutyric Acid Shortens the Life Span of Stroke-Prone Spontaneously Hypertensive Rats

Dietary γ-amino butyric acid (GABA) has been suggested to decrease systolic blood pressure. This study aimed to ex-amine the effects of dietary GABA on the life span of stroke-prone spontaneously hypertensive rats (SHRSPs). In this study, life span was determined for SHRSPs provided 1% NaCl solution or 0.01% GABA in 1% NaCl solution as drinking water. The life span of the GABA-fed group (76.3 ± 1.65 days) was significantly shorter than that of the control group (81.6 ± 0.88 days). The results of this study may not be applicable to humans. Future studies will be necessary to elucidate the mechanism underlying this phenomenon.

Artificial cold exposure induced stroke in renovascular hypertensive rats and its association with cold-inducible RNA binding protein mRNA expression in brain tissue and blood pressure

BACKGROUND： High incidence of stroke at interchange period of autumn and winter was demonstrated by epidemiological survey, and the specific causes should be further investigated. OBJECTIVE： To investigate the influence of artificial cold exposure on the incidence of stroke in renovascular hypertensive rats （RHR）, and analyze the association with blood pressure and cold-inducible RNA binding protein （CIRP） mRNA expression in brain tissue. DESIGN： A completely randomized grouping design, a randomized control animal trial. SETTINGS： Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University; Department of Chemistry, Open laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong. MATERIALS： Male SD rats （n=460）, weighing 80 - 100 g were obtained from Guangdong Province Health Animal Unit. A modified RXZ-300A intelligent artificial climate cabinet （Ningbo Jiangnan Instrument Co. ,Ltd., China）. METHODS： The experiment were processed in the Lab of Neurology, the First Affiliated Hospital of Sun Yat-sen University and the Open Laboratory of Chemical Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, University of Hong Kong from October 2004 to November 2005. Rats （n = 400） were operated to establish 2-kidney 2-clip RHR model as described previously. The sham-operated rats （n =60） served as normotensive controls. Eight weeks later, 300 of RHR were randomly selected according to their systolic blood pressure （SBP） and divided into 3 sub-groups （n =100 per group）： mild hypertensive group （SBP of 160 - 200 mm Hg）, moderate hypertensive group （SBP of 200 - 220 mm Hg） and severe hypertensive group （SBP 〉 220 mm Hg）. Each group was further divided into two groups （n =50） under ACE and non-ACE. Normal sham-operated SD rats （n =60）, SBP 〈 140 mm Hg, were randomly divided into two groups： Sham-operated control group （n =30） under ACE and non-ACE. To establish the ACE and non-ACE treatment, rats were housed individually in artificial climate cabinet, and ACE was designed as three cycles of 12-hour light of 22℃ （7 ： 00 - 19 ： 00） and 12-hour dark of 4℃（19 ： 00 - 7 ： 00）. The non-ACE group was kept at 22℃ throughout the experiment. MAIN OUTCOME MEASURES： Blood Pressure changes were measured and stroke symptom were observed; Expression of the CIRP were examined by reverse transcription-polymerase chain reaction. RESULTS： Finally 360 rats were involved in the analysis of results. ①Incidence of stroke： The incidence of stroke in 2k2c RHR was significantly higher after a three-day intermittent （12-hour） ACE （29.3%） as compared with that in non-ACE （17.3%） （P 〈 0.05）. Furthermore, the severe hypertensive 2k2c RHR （BP 〉 220 mm Hg） was found to have much higher incidence of stroke （66%, 33/50） than the mild （8%, 4/50） and moderate （18%） hypertensive 2k2c RHR. ②CIRP mRNA in brain tissue： ACE treatment stimulated the mRNA expression of CIRP in non-stroke 2k2c RHR but not in stroke 2k2c RHR （P 〈 0.05）. CONCLUSION： High blood pressure and low expression of CIRP are associated with ACE induced stroke.

Effect of Hypertension on Hearing Function,LDH and ChE of the Cochlea in Older Rats

The relationship between the hypertension and the aging process of hearing organ was investigated Twenty Wistar 3-month old rats and 20 Wistar 12-month old rats, 20 spontaneously hypertensive rat stroke-prone (SHRSP) 3-month old rats and 20 SHRSP 12-month old rats free of middle ear infections as observed under otomicroscopy, with normal tympanic membrane and auricle reflex, were selected to be divided into two experimental groups and two control groups respectively The tail artery blood pressure was measured non-invasively The threshold of auditory brainstem response (ABR) was measured by Spirit TM evoked potential meter The LDH and ChE staining in the inner ear was performed and the optical density was analyzed by the HPIAS analysis system The results showed that there was no difference in the ABR thresholds, the activities of LDH and ChE between Wistar 3-month old group and SHRSP 3-month old group ( P >0 05) The mean value of ABR threshold and the activities of LDH and ChE in the Wistar 12-month old group at relevant sections were significantly greater than those in the two 3-month old groups ( P< 0 05), whereas the mean value of ABR threshold and the activities of LDH and ChE in the SHRSP 12-month old group at relevant sections were significantly higher than those in the 3-month old control group ( P< 0 01) It was concluded that presbycusis existed in the Wistar 12-month old group rats The glycogenosis and the abnormal secretion of neural transmitter were discerned after hypertension All the above factors may worsen the aging of the hearing system

Anti-hypertensive effects of rosiglitazone on renovascular hypertensive rats:role of oxidative stress and lipid metabolism

This study investigated the anti-hypertensive mechanismof rosiglitazone in renovascular hypertensive rats,and examined its relationship to oxidative stress and lipid metabolism. The renovascular hypertension was induced by stenosis of the left renal artery. Four groups of rats were selected： control,induced untreated,rosiglitazone（ 20 mg / kg） and captopril（ 10 mg / kg）. After 14 d of administration,compared with induced untreated group,rosiglitazone group reduced the renovascular hypertensive rats ＇ systolic blood pressure and diastolic blood pressure,and decreased total cholesterol（TCH）,triglyceride（TG）,angiotensin II（ Ang II） and angiotensin receptor（ AT1） levels（ P ＆lt; 0. 05）. Meanwhile,rosiglitazone remarkably decreased the levels of malondialdehyde（ MDA） and hydrogen peroxide（ H2O2） while improved the levels of supperoxide dismutase（ SOD） and reduced glutathione（ GSH）. These results suggested that rosiglitazone could effectively decreased the blood pressure in renovascular hypertensive rats,and this might be performed by regulating the activity of angiotensin and the lipid metabolismand improving the oxidative stress.

影像学在肾血管性高血压评估中的进展

肾血管性高血压是继发性高血压最常见的原因之一,是指由肾动脉狭窄引起的高血压。绝大多数肾动脉狭窄是由动脉粥样硬化或纤维肌肉发育不良引起。随着影像学检查技术的快速发展,该疾病的早期检出率不断升高。尤其是各种无创性影像学检查技术在肾动脉狭窄的诊疗过程中起到了至关重要的作用,可早期识别肾动脉、肾脏结构及功能的异常,帮助患者实现早期诊断及获得早期充分治疗。现就影像学在肾动脉狭窄评估中的应用进展进行综述。

Hyponatremic hypertensive syndrome-a retrospective cohort study

AIM To ascertain the frequency of hyponatremic hypertensive syndrome （HHS） in a cohort of children with hypertensive emergency in a tertiary pediatric hospital.METHODS A retrospective review was undertaken among children with hypertensive emergency admitted in our tertiary children hospital between June 2014 and December 2015 with an aim to identify any children with HHS. Three children with HHS were identifed during this period.RESULTS The 3 patients with HHS presented with hypertensive emergency. They were initially managed with Labetalol infusion and thereafter switched to oral anti-hypertensives （combination of Nifedipine sustained release, Hydralazine and Beta Blocker）. All 3 were diagnosed to have unilateral renal artery stenosis. One child was lost to follow up, whereas the other 2 underwent renal angioplasty which was followed with normalization of blood pressure.CONCLUSION Despite activation of renin angiotensin axis secondary to renal artery stenosis, these groups of children have significant hyponatremia. Renal re-vascularisation pro-duces excellent results in most of them.

Effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension

OBJECTIVE: To investigate the inhibitory effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension, and explore the possible mechanism underlying this effect.METHODS: Sixty Wistar rats were randomly divided into six groups: sham operation, model, positive control, and low-, medium-, and high-dose Huai chrysanthemum extract groups(ten rats per group). With the exception of the sham operation group, a renal hypertensive model was established in rats using the 'two-kidney, one clip' method. After 6 weeks, low-, medium-, and high-dose groups were intragastrically administered chrysanthemum extract at 1, 2, or 4 g/kg, respectively, once daily for 4 weeks. The positive control group was administered Kato Pury at 50 mg/kg once daily for 4 weeks,while sham operation and model groups received an equal volume of distilled water once daily for 4 weeks. Blood pressure changes were examined before modeling, 6 weeks after modeling, and after 4 weeks of treatment administration. Ventricular remodeling indexes were measured by high frequency echocardiography after 4 weeks of treatment administration. Pathological changes were observed by hematoxylin and eosin, and Masson’s trichrome staining methods. Collagen type sion were eⅠxa(Col minedⅠ) and type Ⅲ(Col Ⅲ) expres by enzyme-linked immunosorbent assays. Transforming growth factor-β1(TGF-β1), sma mad 3(Smad3),Smad7, Ras homolog gene family, member A(RhoA), and Rho-associated protein kinase 1(ROCK1) protein expression were detected by Western blot.RESULTS: Compared with the model group, chrysanthemum-administered groups and the positive control group showed significant improvement of arterial blood pressure, echocardiography indicators, and degree of myocardial fibrosis(P < 0.05). In addition, these groups exhibited decreased expression of Col Ⅰ, Col Smad3, and increaseⅢ, RhoA, ROCK1, TGF-β1, and d Smad7 expression. Such improvements were most obvious in the high-dose chrysanthemum extract group(P < 0.05).CONCLUSION: Chrysanthemum extract could effectively reduce myocardial fibrosis in rats with renovascular hypertension by a mechanism that potentially involves inhibition of RhoA/ROCK1 and TGF-β1/Smad signaling pathways.

Rationale and study design for one-stop assessment of renal artery stenosis and renal microvascular perfusion with contrast-enhanced ultrasound for patients with suspected renovascular hypertension

Background:Renal artery stenosis (RAS) is always associated with abnormalities in renal microvascular perfusion (RMP).However,few imaging methods can simultaneously evaluate the degree of luminal stenosis and RMP.Thus,this study will aim to evaluate the feasibility of using contrast-enhanced ultrasound (CEUS) for assessing both RAS and RMP to achieve a one-stop assessment of patients with suspected renovascular hypertension. Methods:This will be a single-center diagnostic study with a sample size of 440.Patients with chronic kidney disease (CKD) and suspected of having resistant hypertension will be eligible.Patients with Stages 1–3 CKD will undergo CEUS and computed tomography (CT) angiography (CTA).Values obtained by CEUS and CTA for diagnosing low-grade (lumen reduced by <60%) and high-grade (lumen reduced by ≥60%) RAS will be compared.Moreover,all patients will also undergo radionuclide imaging.The diagnostic value for RAS will be assessed by the receiver operating characteristic curve,including the accuracy,sensitivity,specificity,positive predictive values,negative predictive values,and area under the ROC.Pearson correlation analysis will be performed to assess the association between CEUS findings for RMP and glomerular filtration rate measured by a radionuclide imaging method. Conclusion:The data gathered from this study will be used to evaluate the feasibility of expanding clinical applications of CEUS for evaluation of patients with suspected renovascular hypertension.

Effects of RNA interference targeting angiotensin 1a receptor on blood pressure and cardiac hypertrophy of rats with renovascular hypertension

The aim of this study is to investigate the effects of RNA interference(RNAi)targeting angiotensin 1a receptor(AT1a)on blood pressure and cardiac hypertrophy of rats with renovascular hypertension.Two RNAi plasmids,pAT1a-shRNA1 and pAT1ashRNA2 each carrying a U6 promoter and an AT1aspecific shRNA-coding template sequence corresponding to the sites 928-946,978-996 of the mRNA transcript,and a control plasmid pCon carrying a nonspecific shRNA-coding sequence were constructed.Thirty Sprague-Dawley rats with renovascular hypertension(2-kidney 1-clip)were randomly divided into 5 equal groups:Control group(without any intervention),pAT1a-shRNA1,pAT1a-shRNA2,pCon groups(with injection of the corresponding plasmid 4 mg/kg respectively into the tail vein),and valsartan group(30 mg/kg·d^(-1) by gavage).Three weeks after drug administration,pAT1a-shRNA1,pAT1a-shRNA2 and valsartan respectively resulted in decrease of the tail blood pressure by(15.1±5.4),(16.4±8.4)and(30.6±18.2)mmHg.However,the tail blood pressure increased further by about 25 mmHg in both of pCon and control groups.The carotid artery pressures of pAT1a-shRNA1,pAT1ashRNA2 and valsartan groups were all significantly lower than those of the control and pCon groups.The ratio of left ventricle weight to body weight(LV/BW)of the rats in pAT1a-shRNA1,pAT1a-shRNA2,and valsartan groups decreased significantly than in the control group(P<0.01),similar to those of the normal SD rats(P>0.05).Histopathological examination showed that the myocardiocytes were significantly hypertrophic and the basal membrane of the aorta was significantly thickened in the control group and such changes were alleviated in the pAT1a-shRNA1,pAT1a-shRNA2 and valsartan groups.Compared with the control group,pAT1a-shRNA1 and pAT1a-shRNA2 groups had lowered expression of AT1 receptor(in the myocardium and the thoracic aorta(all P<0.01);however,there were no significant differences in expression levels of AT1 receptor in valsartan and the control groups(P>0.05).We conclude that RNAi targeting AT1a receptor inhibits the development of renovascular hypertension and the accompanying cardiac hypertrophy.RNAi technology may become a new strategy of gene therapy for hypertension.

氯沙坦和培哚普利逆转高血压大鼠心血管重构的比较

目的 比较氯沙坦和培哚普利逆转肾血管性高血压大鼠心血管重构作用及其机制 ,为临床用药提供实验依据。方法 以经典两肾一夹肾血管性高血压大鼠为研究模型。采用鼠尾测压法测定大鼠血压的变化 ;反射免疫分析法测定大鼠血浆血管紧张素Ⅱ含量和肾素活性 ;称量法计算各组大鼠心脏与体重的比值 ;高清晰度数码照相扫描分析技术测定各组大鼠主动脉、肠系膜动脉血管管壁厚度、管壁厚度和管腔内径比值、管壁面积和管腔面积比值来估计两类药物对心血管重构的影响。结果 高血压大鼠心脏与体重的比值、主动脉、肠系膜动脉血管管壁厚度和管腔内径比值、管壁面积和管腔面积比值与正常大鼠相比明显增大 (P <0 0 1) ,给予氯沙坦 (2 0mg·kg-1)或培哚普利 (3mg·kg-1)治疗后 ,上述各项指标基本接近正常水平 ,与非用药组相比具有显著差异 (P<0 0 1)。结论 氯沙坦和培哚普利均能明显降低高血压大鼠血压 ;长期应用较低剂量氯沙坦和培哚普利均能有效逆转高血压大鼠病理性心血管重构 ,两药存在等效性。

珍菊降压片对肾性高血压大鼠血压的影响

目的 观察珍菊降压片 (ZJ)及其西药组分对肾性高血压大鼠 (RHR)血压和停药后血压反跳的影响 ,并研究其对RHR血脂与血脂蛋白的影响。方法 左肾动脉狭窄法建立两肾一夹高血压大鼠模型 ;无创尾套法测量清醒RHR尾动脉收缩压。结果 与模型组比较 ,ZJ组 (4 0mg·kg-1,80mg·kg-1,16 0mg·kg-1)及西药组分组 (1.79mg·kg-1,相当于全药中剂量组 )对RHR有明显的降压作用 (P <0 .0 1) ;ZJ各剂量间降压作用无显著性差异 ;同比剂量组(80mg·kg-1)与西药组分组 (1.79mg·kg-1)降压作用无显著性差异 (P >0 .0 5 ) ;与西药组分组 (1.79mg·kg-1)比较 ,ZJ未出现血压反跳现象 (P <0 .0 5 ) ;ZJ对血脂和血脂蛋白无显著性影响 (P >0 .0 5 )。结论 珍菊降压片有良好的抗高血压作用 。