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As of August 16,2021,there have been 207,173,086 confirmed cases and 4,361,996 deaths due to the coronavirus disease(COVID-19),and the pandemic remains a global challenge.To date,no effective and approved drugs are available for the treatment of COVID-19.Angiotensin-converting enzyme 2(ACE2)plays a crucial role in the invasion into host cells by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the etiological agent of COVID-19.Notably,ACE2 density is influenced by medical con-ditions,such as hypertension,or by drugs,including angiotensin-converting enzyme inhibitors(ACEIs)and angiotensin receptor blockers(ARBs),which can change the fate of SARS-CoV-2 infectivity.ACE2 is a target for these drugs and can be manipulated to limit the viral entry and replication within the cells.Different strategies aimed at blocking ACE2 with small molecules,peptides,and antibodies,or by neutralizing the virus through its competitive binding with human recombinant soluble ACE2(hrsACE2)are currently under investigation.In this article,we review the current state of knowledge that em-phasizes the need to find effective therapeutic agents against COVID-19 by exploiting ACE2 as a potential target.The increased soluble ACE2 levels and the application of hrsACE2 in patients with COVID-19 can be implemented to control the disease.It has not yet been established whether hypertension and other comorbidities,independent of age,have a direct role in COVID-19.Therefore,the use of renin-angiotensin system inhibitors,ACEls and ARBs,should not be discontinued during COVID-19 treatment.
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Background: Drug utilization pattern studies helps to screen, assess and propose appropriate modifications in prescription practices, this would help to make patient care rational and cost effective. Study was intended to analyse the drug prescribing pattern for treatment of Ischemic heart disease using WHO indicators.Methods: This is a cross sectional observational study conducted on ischemic heart disease patients admitted at inpatient department of medicine in a tertiary care teaching hospital. The study consisted of analysis of drug utilization pattern of prescribed drugs.Results: IHD was more commonly seen in males (70.06%) than females (29.94%). IHD was most commonly seen in patients of age group of 61-70 year. Drugs prescribed to patients belong to various therapeutic classes ranging from anti-platelets, anticoagulants, anti-anginal, antithrombin, thrombolytic, hypolipidemics. The most commonly prescribed therapeutic class of drugs was antiplatelet (86.26%) followed by hypolipidemic (82.25%) and ACE inhibitors drugs (46.60%). Average number of drugs per encounter was 7.70. Drugs were prescribed by their generic names were 29.99%. Out of total study group 22.06% patients were prescribed at least one antibiotic. Injections were prescribed only in 1392 (27.86%) out of 4995 drugs. Of total drugs 3270 (65.45%) of drugs were from National List of Essential Medicines-2016 (NLEM -2016) and 2774 (55.53%) drugs prescribed were from WHO-EML-2016.Conclusions: Risk of artery disease increased with increasing age. IHD was more common in males than females. The most commonly prescribed drug classes in Ischemic heart disease were anti-platelet drugs followed by hypolipidemic agents.
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Objective: To study the impact of aceclofenac on antihypertensive action of amlodipine and ramiprilin hypertensive patients with osteoarthritis in an open label case control prospective study. Methods: This was an open label case control prospective study. Hypertensive patients on either amlodipine or Ramipril were included in control groups. A total of 120 patients were included in the study and divided into 4 groups: Group A- Hypertensivepatients on Ramipril; Group B – Hypertensive patients with concomitant osteoarthritis taking Aceclofenac and Ramipril; Group C– Hypertensive patients on Amlodipine and Group D- Hypertensive patients with concomitant osteoarthritis taking Aceclofenac and Amlodipine. Results: At the end of the first month (phase I), the ramipril subgroup in the control group had a mean systolic blood pressure of 136.73±3.80 which was an 8.19% decrease from the baseline and it was found significant (p<0.05). The systolic blood pressure measurements at the end of the second month (phase II) in the control groups revealed further fall in mean systolic blood pressure. The cases of osteoarthritis on aceclofenacand ramiprilshowedan increase in BP. The mean Systolic BP was 159.2 ± 5.816.An increase of 9.74%from the base line and 16.09% was noted at the end of phase-I (P<0.5). Patients on aceclofenac and amlodipine in contrast showed a fall in BP from base line in phase 0 and their mean systolic blood pressure at positive in of second month of phase-II was 142.07± 2.43 about 1.88% fall baseline and 2.94% increase in BP compared to Phase-I. Almost similar observations were recorded for diastolic blood pressure. Conclusion: The interaction of NSAIDs on the antihypertensive action of the ACE inhibitors is significantly greater than their blunting action on the calcium channel blockers.
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Tityus serrulatus venom (Ts venom) is a complex mixture of several compounds with biotechnological and therapeutical potentials, which highlights the importance of the identification and characterization of these components. Although a considerable number of studies have been dedicated to the characterization of this complex cocktail, there is still a limitation of knowledge concerning its venom composition. Most of Ts venom studies aim to isolate and characterize their neurotoxins, which are small, basic proteins and are eluted with high buffer concentrations on cation exchange chromatography. The first and largest fraction from carboxymethyl cellulose-52 (CMC-52) chromatography of Ts venom, named fraction I (Fr I), is a mixture of proteins of high and low molecular masses, which do not interact with the cation exchange resin, being therefore a probable source of components still unknown of this venom. Thus, the present study aimed to perform the proteome study of Fraction I from Ts venom, by high resolution mass spectrometry, and its biochemical characterization, by the determination of several enzymatic activities. Methods: Fraction I was obtained by a cation exchange chromatography using 50 mg of crude venom. This fraction was subjected to a biochemical characterization, including determination of L-amino acid oxidase, phospholipase, hyaluronidase, proteases activities and inhibition of angiotensin converting enzyme (ACE) activity. Fraction I was submitted to reduction, alkylation and digestion processes, and the tryptic digested peptides obtained were analyzed in a Q-Exactive Orbitrap mass spectrometer. Data analysis was performed by PEAKS 8.5 software against NCBI database. Results: Fraction I exhibits proteolytic activity and it was able to inhibit ACE activity. Its proteome analysis identified 8 different classes of venom components, among them: neurotoxins (48%), metalloproteinases (21%), hypotensive peptides (11%), cysteine-rich venom protein (9%), antimicrobial peptides (AMP), phospholipases and other enzymes (chymotrypsin and lysozymes) (3%) and phosphodiesterases (2%). Conclusions: The combination of a proteomic and biochemical characterization strategies leads us to identify new components in the T. serrulatus scorpion venom. The proteome of venom´s fraction can provide valuable direction in the obtainment of components in their native forms in order to perform a preliminary characterization and, consequently, to promote advances in biological discoveries in toxinology.(AU)
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Animals , Scorpion Venoms , Biological Products , Proteome , Metalloproteases , Neurotoxins , Phospholipases , EnzymesABSTRACT
Background: This study was aimed to analyze the drug utilization pattern in the management of hypertension in diabetic patients.Methods: A prospective, observational and non interventional study was conducted in 100 diabetic hypertensive patients admitted in medicine wards at Dhiraj Hospital. Patients who signed informed consent form were only included in the study. All the data were recorded from patients’ case files and analyzed.Results: Of enrolled 100 patients, 69 (69%) were male and 31 (31%) were female and maximum number of the patients (42%) were found in the age group of 51-60 years. Out of 100 admitted patients, 75% patients were treated with single antihypertensive agent, 20% were treated with combination of two antihypertensive agents while only 5% were administered more than two antihypertensive agents. As a single antihypertensive agent, most commonly prescribed was ACE inhibitors (32%), Calcium Channel Blockers (23%), Angiotensin Receptor Blockers (12%) and ?1 blockers (8%).Conclusions: There was poor awareness among the patients regarding control of hypertension, regular follow up, medication adherence etc. However, two third of diabetic patients had achieved blood pressure target control and ACE inhibitor remained first choice of drug for hypertension in diabetes in this study.
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Background: Hypertension with dislipidemia is becoming a common morbidity, since ACE inhibitors are the first line of antihypertensive drugs so present study was undertaken with the aim to evaluate the possible effects of ACE inhibitor on lipid profile in albino rabbits.Methods: The study was conducted in the Department of Pharmacology and Therapeutics, GSVM Medical College, Kanpur. Rabbits were divided into 2 groups with 6 in each group. Rabbits of Group I was given Lisinopril in dose of 0.25mg/kg and of group II was given Perindopril in dose of 0.20mg/kg for a period of 6 weeks. Lipid profile estimation (Serum Total cholesterol, serum HDL, serum LDL, serum Triglycerides and serum VLDL) was done at day 0, 7, 21 and 45 respectively.Results: After analysis Rabbits of group-I (Lisinopril) showed 3.1% decrease in serum cholesterol level at 45th day (P<0.001). Serum HDL level increased by 6.4% and 14.3% at day 21 and 45 respectively (P<0.05). Increase in serum Triglyceride level was 2.6% at day 45 (P>0.05). Serum LDL level decreases by 4.4% and 8.6% at day 21 and 45 respectively (P<0.001). There was no significant change in Serum VLDL level. Rabbits of group- II (Perindopril) showed decreased total cholesterol levels by 2.6% (P<0.05). There was an increase in HDL level by 6.8 % at day 45(P<.05). Triglycerides and VLDL levels were not significantly altered while serum LDL level decreases by 6.7% at day 45 (P<0.01).Conclusions: From our study it was concluded that Lisinopril had a favourable effect on serum lipid profile by decreasing total cholesterol, increasing serum HDL level. It may increase triglycerides, decrease LDL. Perindopril increase serum HDL and decreases LDL, there is no significant change in cholesterol, TG and VLDL levels.
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Background: Regression of ventricular hypertrophy is the restoration of normal ventricular structure and physiology after the hypertrophy has developed. It has been clearly demonstrated that once left ventricular hypertrophy (LVH) is diagnosed, it represents a strong blood pressure independent risk factor for cardiovascular morbidity and mortality. Aims and Objectives: The aim of this study is to compare the effectiveness of different anti-hypertensive agents in reducing LVH in Bangladeshi population. Methods: A prospective observational study was carried out to detect the regression of left ventricular hypertrophy in hypertensive Bangladeshi population using high resolution M-mode echocardiographic study in 110 patients with clinically diagnosed hypertension were included in this study but later 15 patients failed to attend clinic for subsequent follow up. Hence, total number of patient was 95; The mean age (±SD) of these patients were 42 ± 5 and male-female ratio was 8.5:1.5. Out of these 95 patients, 20 were included in Beta-blocker(BB) group, 14 in Angiotensin converting enzyme inhibitor(ACEi) group, 20 in Beta-blocker(BB) + Diuretic(DD), 14 were recruited in Angiotensin enzyme inhibitor(ACEi) + Diuretics(DD) and 13 in Beta-blocker and ACEi group and 14 in BB + ACEI + Diuretic group. We followed these patients after 8 weeks, 6 months, 1 year and 2 years in our clinic. A baseline M-mode echocardiography was done to document LVH. During this follow up, we have measured IVSd, PWd, LVIDd and LVIDs and statistically analyzed SD and P-value for each group by using SPSS software. The duration of study was from 01.07.2005 to 30.06.2008. Results: Comparison of Beta blocker alone and ACEi alone group for LVH regression showed a P value of 0.59. Although this figure did not show a statistically significant value if we increase number of patients in both group we would expect a statistically significant P value in favour of ACEi. BB plus diuretics was compared with ACEi plus Diuretics which showed P value of 0.85. We also compared BB plus ACEi group with BB plus ACEi plus DD for LVH regression which showed a P value of 0.79. Conclusion: Among three groups of anti-hypertensive drugs, angiotensin converting enzyme inhibitor(ACEi) alone has been found to be most effective as compared to Beta blockers when used alone than in combination groups with (Beta blocker plus ACEi plus Diuretics or Beta blocker plus ACEi). Although, these figure was not found statistically significant a clear benefit has been shown in all groups in terms of LVH regression and essentially if the power or size if this is increased a statistically significant value of LVH regression value may be observed in all these groups.
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Lowering of blood pressure itself lowers urinary protein excretion rate and slows rate of GFR decline in chronic renal disease. There are data that suggests that ACE inhibitors improve glomerular barrier size selective function in experimental and human renal disease by directly lowering the mean dimensions of large unselective pores. A reduction in urinary protein excretion correlates with improved renal function and survival in non diabetic and diabetic renal disease. The initial reduction in rate of excretion inversely correlates with long term preservation of renal function in patient without diabetes treated with angiotensin converting enzyme inhibitors. In this study of 97 patients, the results showed that antihypertensive regimens of ace inhibitors group were more effective than non ace inhibitor in slowing progression of non diabetic chronic kidney disease. The presence of proteinuria in non diabetic chronic kidney disease is a strong indication for treatment with ace inhibitors. A brief epidemiology and pathophysiology is also discussed to understand the role of hypertension and proteinuria in chronic kidney disease.
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Angiotensin-converting enzyme (ACE) inhibitors have non-hemodynamic, pleiotropic effects on the immune response. The effects of ACE inhibitors on the production of cytokines and T-cell functions are well established. However, little is known on the effects of these medicines on humoral response to foreign antigens. In this study, we investigated the effect of enalapril treatment on ovalbumin (OVA)-specific IgG1 and IgG2c production in mice determined by ELISA. Two groups of 8-week-old C57BL/6 females mice (3–4/group) were subcutaneously immunized with OVA (10 μg/animal) in presence of Alhydrogel (1 mg/mouse) and boosted at day 21. The mice were treated with enalapril (5 mg/kg daily, po) or were left without treatment for one month. The animals were bled from the orbital plexus on days 0, 7, 14, 21, and 28 after the first immunization and the sera were stored at –20°C until usage. OVA-specific serum IgG1 and IgG2c were determined by ELISA using serum from each individual animal. The results showed that enalapril significantly increased anti-OVA serum IgG2c in the secondary response without affecting IgG1 synthesis. These data expand our understanding on the properties of enalapril on the immune response, including antibody production.
Subject(s)
Animals , Female , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalapril/pharmacology , Immunity, Humoral/drug effects , Immunoglobulin G/blood , Ovalbumin/immunology , Antibody Formation/drug effects , Immunoglobulin G/immunology , Mice, Inbred C57BL , Models, Animal , Th1 Cells/immunology , Th2 Cells/immunologyABSTRACT
Migraine is a chronic neurological disorder characterized by recurrent moderate to severe headaches, associated with a number of autonomic nervous system symptoms. Migraine constitutes 16% of primary headaches affecting 10-20% of general population according to International Headache Society. Typically the headache is unilateral (affecting one half of the head) and pulsating in nature, lasting from 2 to 72 hours. Associated symptoms may include nausea, vomiting, photophobia, phonophobia and the pain is generally aggravated by physical activity. Globally, approximately 15% of the population is affected by migraine at some point in life. Initial recommended management is with simple analgesics such as ibuprofen and acetaminophen for the headache, an antiemetic for the nausea, and the avoidance of triggers. Specific agents such as triptans or ergotamines may be used by those for whom simple analgesics are not effective. All the already available drugs have certain limitations. Either they are unable to produce complete relief or 30-40% patients are no responders or drugs produce adverse effects. A new class of drugs like angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor antagonists have recently been studied for their off label use in prophylaxis of migraine. Studies done so far, have shown results in favour of their clinical use because of the ability to reduce number of days with headache, number of days with migraine, hours with migraine, headache severity index, level of disability, improved Quality of life and decrease in consumption of specific or nonspecific analgesics. This article reviews the available evidence on the efficacy and safety of these drugs in prophylaxis of migraine. Relevent literatures were chosen, examining the efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for migraine prophylaxis.
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Candesartan is classified as an angiotensin II receptor type 1 antagonist. Angiotensin II receptor type 1 antagonists are widely used in treatment of diseases like hypertension, heart failure, myocardial infarction and diabetic nephropathy. Candesartan is an orally active lipophilic drug and possesses rapid oral absorption. It causes reduction in blood pressure and is used in treatment of hypertension. It is also used in the treatment of congestive heart failure and given as prophylaxis to reduce the severity and duration of migraine. Candesartan cilexetil, a prodrug of Candesartan, is available in the market under the trade names- Blopress®, Atacand®, Amias® and Ratacand®. Candesartan is also available in a combination formulation with a low dose thiazide diuretic, invariably hydrochlorothiazide, to achieve an additive antihypertensive effect. This paper reviews the pharmacological and pharmaceutical properties of Candesartan. Candesartan could be an attractive target for the generic industries.
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Angiotensin II Receptor type 1 antagonists have been widely used in treatment of diseases like hypertension, heart failure, myocardial infarction and diabetic nephropathy. Their beneficial effects are related to inhibition of Angiotensin II by blockade of AT1 receptor. Valsartan is an orally active Angiotensin II receptor type 1 antagonist which causes reduction in blood pressure and is used in treatment of hypertension. It was first developed by Novartis and has a wide market in the developed and the developing countries. It is also available in combination with other antihypertensive drugs. It is a lipophilic drug and possesses moderate onset of action than other drugs of the same category. The drug is a very good target for the generic industries. This review evaluates the pharmacological properties of Valsartan and its efficacy and tolerability in the treatment of patients with hypertension. A brief discussion has also been made on the current and future aspects of the drug in the market.
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Background To document the pharmacotherapy of chronic heart failure (CHF) and to evaluate the adherence to treatment guidelines in Australian population.Methods The pharmacological management of 677 patients (female 46.7%,75.5±11.6 years) with CHF was retrospectively analyzed.Results The use of angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB) and fl-blockers were 58.2%and 34.7%,respectively.Major reasons for non-use of ACE inhibitors/ARBs were hyperkalemia and elevated serum creatimne level.For patients who did not receive β-blockers,asthma and chronic obstructive pulmonary disease were the main contraindications.Treatment at or above target dosages for ACE inhibitors/ARBs and β-blockers was low for each medication (40.3% and 28.9%,respectively).Conclusions Evidenced-based medical therapies for heart failure were under used in a rural patient population.Further studies are required to develop processes to improve the optimal use of heart failure medications.
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Background & objective: The efficacy of the combination of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors in patients of type 1 diabetes mellitus (DM) with nephropathy is debatable. The antialbuminuric efficacy of dual blockade in patients of type 1 DM with micro- or macroabuminuria were evaluated. Methods: In this open label observational study 30 patients (20 male 10 female) with type 1 DM were included who were initially treated with telmisartan 80 mg for eight weeks followed by addition of ramipril 10 mg for a further eight weeks. Albuminuria reduction was studied at the end of each phase. Results: Therapy with telmisartan for 8 wk resulted in a 39 per cent (P<0.01) reduction in albumin excretion rate (AER). Combination therapy with telmisartan and ramipril produced a further reduction in AER of 33.4 per cent (P<0.01), amounting to a total AER reduction of 59 per cent (P<0.001). Dual blockade was more effective in the group of macroalbuminuric as compared to microalbuminuric subjects (P<0.05). Telmisartan produced a significant reduction in SBP (P<0.05). The addition of ramipril produced a further reduction in BP, the total reduction being 10.3 in SBP and 7.2 mmHg in DBP (P<0.001 for both). There was an increase in mean serum potassium of 0.39 mmol/l (P<0.01) from baseline at the end of the study period and two patients had hyperkalemia > 5.5 mmol/l with dual blockade. Interpretation & conclusion: Dual blockade with ramipril enhanced the antialbuminuric efficacy of telmisartan and further reduced blood pressure. The effect of dual blockade was more pronounced in the macroalbuminuric subjects and it was well tolerated. However, careful monitoring of serum potassium is required.
Subject(s)
Albumins/metabolism , Albuminuria/drug therapy , Albuminuria/etiology , Angiotensin II Type 1 Receptor Blockers/pharmacology , Angiotensin II Type 1 Receptor Blockers/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Benzimidazoles/therapeutic use , Benzoates/therapeutic use , Blood Pressure/drug effects , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/complications , Drug Combinations , Female , Humans , Male , Potassium/blood , Ramipril/therapeutic use , Statistics, NonparametricABSTRACT
La nefropatía diabética constituye una patología con elevada morbimortalidad y es la principal causa de ingreso a tratamiento de diálisis. Esta revisión tiene por objeto describir en forma concisa y práctica aquellos aspectos más relevantes en la evaluación y tratamiento de la nefropatía diabética, sin dejar de lado los aspectos preventivos cuyo respaldo de evidencia es robusto. Si bien está escrito desde la óptica del nefrólogo no debe perderse de vista una concepción y manejo integral del enfermo.
Diabetic nephropathy is the main cause of end stage renal failure. This review, intended to the general practitioner, aims to describe in a concise form the most relevant issues in the management of diabetic nephropathy. Although written from the stand point of view of the nephrologist, a multidisciplinary approach is warranted.
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Humans , Diabetic Nephropathies/diagnosis , Diabetic Nephropathies/drug therapy , Albuminuria , Arterial Pressure , Antihypertensive Agents/therapeutic use , Blood Glucose , Creatinine/urine , Glomerular Filtration Rate , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Nutritional Status , Diabetic Nephropathies/physiopathologyABSTRACT
Usage of natural substances as therapeutic agents in modern medicine has sharply declined from the predominant position held in the early decades of last century, but search for bioactive molecules from nature (plants, animals, microflora) continues to play an important role in fashioning new medicinal agents. With the advent of modern techniques, instrumentation and automation in isolation and structural characterisation, we have on hand an enormous repository of natural compounds. In parallel to this, biology has also made tremendous progress in expanding its frontiers of knowledge. An interplay of these two disciplines constitutes the modern thrust in research in the realm of compounds elaborated by nature. The purpose of this article is to underline how natural products research continues to make significant contributions in the domain of discovery and development of new medicinal products. It is proposed to present the material under several heads, each of which has made natural products research relevant in the search for new and better medication.
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Introdução: A preservação a frio geralmente é utilizada para minimizar a injúria renal durante a preservação. Testamos se a adição de sinvastatina, captopril, e ramipril à solução de Euro-Collins (EC) ou o pré-tratamento de rins de ratos doadores com ramipril e/ou sinvastatina poderia reduzir a injúria da preservação renal. Métodos: Inicialmente, adicionamos ramipril e sinvastatina à solução de EC, contendo fragmentos de rins de ratos que foram preservados a frio por 24 horas (n=6). O dano tecidual foi avaliado pela liberação de desidrogenase lática (DHL). In vivo, ramipril, por gavagem, e/ou sinvastatina, intraperitonealmente, foram administrados aos ratos doadores 18h antes da nefrectomia.Fragmentos renais foram estocados a frio em EC durante 24h ou 48h. O dano tecidual foi avaliado, utilizando a liberação de DHL, substâncias reativas ao ácido tiobarbitúrico (TBARS), teste do MTT e pelo exame morfológico após 0, 24, e 48h (n=10). Concomitantemente, captopril foi acrescentado à solução de EC e fragmentos adicionais dos rins de ratos controles foram estocados a frio durante 24h e 48h, com dano tecidual avaliado por liberação de DHL e exame histológico. Resultados: A adição de ramipril e sinvastatina à solução de EC não afetou a viabilidade dos fragmentos renais (p>0,05). A adução de captopril na solução de EC também não melhorou a viabilidade durante a preservação a frio, avaliada pela liberação de desidrogenase lática e pelo escore histológico (p>0,05). O pré-tratamento dos doadores renais com ramipril e/ou sinvastatina não alterou significativamente o MTT, MDA, DHL ou escores histológicos. Discussão: Inibidores da ECA e estatinas protegem contra a injúria da isquemia-reperfusão (I/R) após pré-tratamento por alguns dias e reduzem o estresse oxidativo e marcadores inflamatórios e poderiam melhorar a capacidade antioxidante da solução de EC...
Background: Cold storage is generally used to minimize kidney injury during preservation. We tested whether or not addition of simvastatin, captopril, and ramipril in the Euro-Collins solution (EC) or pre-treatment of rat kidney donors with ramipril and/or simvastatin reduced preserved kidney injury.Methods: We first added ramipril and simvastatin to EC with rat kidney fragments that were cold-stored for 24 hours (n=6). Tissue damage was assessed by lactate dehydrogenase (LDH). In vivo, ramipril, by gavage, and/or intraperitoneal simvastatin , were administered to donor rats 18h before nephrectomy. Kidney fragments were cold-stored in EC for 24h or 48h. Tissue damage was assessed by LDH release, TBARS, MTT-assay, and by morphologic assessment at 0, 24, and 48h (n=10). Concomitantly, captopril was added to EC and additional fragments of control rat kidneys were coldstored for 24 and 48h, with damage assessed by LDH release and histology. Results: The addition of ramipril and simvastatin to EC solution did not change the viability of rat kidney fragments (p>0.05). The addition of captopril in the EC solution also did not improve cold-storage viability, as assessed by LDH release levels and histological scores (p>0.05). Pre-treatment of kidney donors with ramipril and/or simvastatin did not significantly change MTT, MDA, LDH levels or histological scores.Discussion: ACEIs and statins protect against organ I/R injury after donor pre-treatment for a few days and reduce oxidant stress and inflammatory markers, and could improve the antioxidant capacity of EC solution. In the tested concentrations, inclusion of captopril, ramipril, and simvastatin in the EC solution did not improve the preservation quality of cold-stored rat kidney fragments...
Subject(s)
Animals , Antihypertensive Agents/analysis , Ischemia/therapy , Rats , SimvastatinABSTRACT
A 27-year-old woman presented with severe hypertension and nephrotic range proteinuria. She had a blunt renal trauma 4 weeks ago and was treated by the left main renal artery ligation. The plasma renin activity, angiotension II and aldosterone levels were very high and the abdominal angiography showed the occlusion of the left main renal artery with relatively preserved blood flow in upper pole of the left kidney. In captopril renal scan, relatively preserved perfusion in upper pole of left kidney was further compromised after captopril administration. The massive proteinuria and hypertension were improved after combination of ACE inhibitor and angiotensin II type 1 receptor blocker treatment.
Subject(s)
Adult , Female , Humans , Aldosterone , Angiography , Angiotensin II , Angiotensin-Converting Enzyme Inhibitors , Angiotensins , Captopril , Hypertension , Hypertension, Renovascular , Kidney , Ligation , Perfusion , Plasma , Proteinuria , Receptor, Angiotensin, Type 1 , Renal Artery , ReninABSTRACT
BACKGROUND AND OBJECTIVES: Ramipril and candesartan have decreased the incidence of new onset diabetes in large scale randomized clinical studies. Because ramipril and candesartan have distinct mechanisms of action in the renin angiotensin aldosterone system, we hypothesized that combination therapy would have additive beneficial metabolic effects in patients with hypertension. SUBJECTS AND METHODS: Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each being 2 months). RESULTS: Ramipril, combination therapy or candesartan significantly increased the plasma adiponectin levels relative to the baseline measurements by 17+/-6% (p=0.038), 25+/-5% (p<0.001), and 14+/-6% (p=0.016), respectively. Combination therapy significantly increased the plasma adiponectin levels more than either ramipril or candesartan alone (p=0.020 by ANOVA). Only combination therapy significantly increased the QUICKI level relative to the baseline measurements (p=0.002). There were no significant correlations between these changes of the metabolic parameters and reduction of the systolic blood pressure (-0.288< or =r< or =0.284) and reduction of the diastolic blood pressure (-0.282< or =r< or =0.190). On multivariate analysis, only the change of adiponectin levels was an independent predictor of the changes in the QUICKI levels (beta=1.549, p=0.040) following combination therapy. CONCLUSION: Ramipril in combination with candesartan increases the plasma adiponectin levels to a greater extent than monotherapy with either drug alone. Only combination therapy significantly improves insulin sensitivity relative to the baseline measurements. The only predictor for the improvement of insulin sensitivity is the increase of plasma adiponectin levels by combination therapy.
Subject(s)
Humans , Adiponectin , Angiotensin-Converting Enzyme Inhibitors , Arm , Blood Pressure , Hypertension , Incidence , Insulin Resistance , Insulin , Multivariate Analysis , Plasma , Ramipril , Renin-Angiotensin SystemABSTRACT
PURPOSE: Clinically, bladder outlet obstruction (BOO) causes not only obstructive symptoms but also overactive bladder symptoms which partially result from the increase of electrical coupling in the bladder. This study was performed to determine the effect of angiotensin converting enzyme (ACE) inhibitor on connexin (Cx) expression in overactive bladder caused by BOO in a rat model. MATERIALS AND METHODS: Fifty Sprague-Dawley rats were used for this study and divided into control (10 rats) and experimental (40 rats) groups. Partial obstruction was induced in the experimental group which was divided into two subgroups of 20 rats each: one group administered with ACE inhibitor (ACE inhibitor treated group) and the other without administration (obstruction group). Cystometrograms (CMG) were performed 2 weeks after BOO. The bladders of each group were dissected out and underwent staining for Cx26 and Cx43. RESULTS: On CMG, there was a significant decrease in contraction interval of the obstructive group compared with the control group. The ACE inhibitor treated group showed an increase in contraction interval compared with the obstruction group but a decrease in contraction interval compared with the control group (p<0.05). On immunohistochemical staining, Cx26 was localized in the mucosa and Cx43 in the mucosa and muscle layer. The staining intensity of Cx26 and Cx43 was increased in the obstructive group compared with the control group, but decreased in the ACE inhibitor treated group compared with the obstruction group. CONCLUSIONS: ACE inhibitor decreased the expression of Cx and relieved the overactive bladder symptom. Therefore, ACE inhibitor could be used as alternative agent for the treatment of overactive bladder associated with BOO.