Chronic and acute effects of kefir: the role of angiotensin converting enzyme inhibition instead of nitric oxide balance

Probiotic consumption promotes numerous health benefits. The aim of this study is 1) to evaluate the antihypertensive effect of kefir in a hypertension rat model caused by the administration of the nitric oxide synthesis inhibitor, L-NAME, and 2) to evaluate the acute angiotensin converting enzyme (ACE) inhibitory activity of the soluble nonbacterial fraction (SNBF) of kefir. To develop the first aim, male rats were separated into three groups: control group (C) treated with 0.3 mL/100 g of milk; L-NAME group (LN) received 10 mg/kg of said inhibitor; and Kefir group (K) treated with 0.3 mL/100 g of kefir plus L-NAME (10 mg/kg of said inhibitor). The treatments were given by oral gavage twice a day for four weeks. For the second aim"instead additionally, male rats received angiotensin I (in bolus) in three doses (Ang I: 0.03, 3 and 300 µg/kg) and were separated into two groups: a) received captopril (30 mg/kg i.v.) and b)received SNBF of kefir (5 mL/kg i.v.). Blood pressure were evaluated before and after Ang I. After treatment, hemodynamic parameters were evaluated, heart weight was recorded, and body weight gain was calculated. SNBF of kefir did not decrease the blood pressure for L-NAMEtreated animals, and no changes were observed in the cardiac parameters. However, the SNBF of kefir demonstrated acute inhibition of ACE in vivo similar to that of captopril. Thus, our results suggest that kefir may improve human cardiovascular systems by using mechanisms independent of nitric oxide syntheses. Additionally, the renin angiotensin system is probably the most important system involved in kefir effect regarding hypertension.

Isolation and characterization of antihypertensive peptides from soy bean protein

Proteins and peptides are the most diverse biomolecules found in nature and make our interest due to their wide applications in food and pharmaceutical industry. Angiotensin Converting Enzyme (ACE) plays a major role in controlling blood pressure. The inhibition of ACE with peptides is a main target in the regulation of hypertension. The objective of the present study was to investigate the therapeutic potential of soy bean. This was accomplished by isolation of ACE inhibitory peptides using response surface methodology (RSM) and characterization of these bioactive peptides by mass spectrometry. 31 hydrolyzed fractions were isolated and evaluated for their ACE inhibition potential. Hydrolyzed fraction having highest ACE inhibitory activity was characterized by liquid chromatography-mass spectrometry (LC-MS) technique. RSM results showed maximum ACE inhibition potential (64%) by hydrolyzate was obtained at 45 ºC temperature, pH 8.0, E/S 0.2 in 2 hours hydrolysis time. Results of LC-MS analysis revealed Ser-Gly, Ser-Pro, Met-Ala, His-Ala, Lys-Pro, Phe-Thr, Met-Leu, Pro-Arg, Ala-Pro-Val, Pro-Ala-Leu, Val-Met-Gly, Pro-Leu-Val, Pro-Pro-Gln, His-Arg-Gly, Ser-Phe-Val-Leu, Ala-Val-His-Try, Arg-Thr-Val-Arg, His-His-Tyr-Leu-Val, Asp-Gly-Ala-Cys-Ser-Ala-Asn and MetVal-Thr-Gly-Pro-Gly-Cys-His bioactive peptides in hydrolyzed fraction of soy bean. Our data provide evidence that response surface methodology is a good approach for isolation of antihypertensive bioactive peptides with more potent activity as nutraceuticals or pharmaceuticals. Therefore soy bean can be use for industrial production of pharmaceutical grade natural medicines for handling high blood pressure.

Total flavonoids from Ampelopsis megalophylla suppress proliferation of vascular smooth muscle cells in vivo and in vitro

ABSTRACT Various benefits of flavonoids for ameliorating cardiovascular diseases have been demonstrated. However, the lowering effects on blood pressure caused by antiproliferative potentials of flavonoids in vascular smooth muscle cells are rare. In this study, the antihypertensive effects of total flavonoids from Ampelopsis megalophylla were investigated. The dynamic pressure values and the rate of media thickness versus lumen diameter were measured by the tail-cuff system and H&E staining in vivo, respectively. The mRNA expressions of ACE, Ang II, eNOS, c-Myc, cyclin D1 and p27Kip1 in thoracic aorta or A7r5 cells were measured by qPCR, respectively. The protein expressions of c-Myc, Cyclin D1, p27Kip1 and ß-catenin in tissues or A7r5 cells were measured by Western blot assay. Total flavonoids of A. megalophylla (TFAM) reduced the expressions of ACE and Ang II, and elevated the content of eNOS in thoracic aorta cells of SHRs. Furthermore, TFAM decreased the mRNA and protein expressions of c-Myc and cyclin D1 by repressing the Wnt/ß-catenin-mediated TCF/LEF transcriptional activation both in vivo and in vitro, which is synergetic with the up-regulation of p27Kip1 expression. Our study provided evidence for developing flavonoids from A. megalophylla as herbal supplements to prevent against cardiovascular diseases by suppressing vascular remodeling

Comparação dos efeitos do benazepril e da losartana sobre a função endotelial e a rigidez arterial em pacientes diabéticos com hipertensão não controlada por anlodipino / Comparison of benazepril and losartan on endothelial function and vascular stiffness in hypertensive diabetic patients with hypertension not controlled by amlodipine

Em pacientes hipertensos e diabéticos, o sistema renina-angiotensina-aldosterona está relacionado com disfunção endotelial, rigidez vascular e aterosclerose. As principais medicações disponíveis para a inibição desse sistema são os inibidores da enzima conversora de angiotensina e os bloqueadores do receptor AT1 de angiotensina. A maioria das diretrizes internacionais faz as mesmas recomendações para as duas classes, mas diferenças no seu mecanismo de ação podem ter relevância clínica. O objetivo principal foi comparar benazepril e losartana em pacientes hipertensos e diabéticos com pressão arterial não controlada por anlodipino, analisando parâmetros inflamatórios (proteína C reativa), da função endotelial (através da dilatação mediada por fluxo da artéria braquial) e de rigidez vascular (através da velocidade da onda de pulso e das pressões aórticas). O objetivo secundário foi, através de uma análise post-hoc, pesquisar se há interação entre as estatinas e os inibidores do sistema renina-angiotensina-aldosterona. Pressão arterial, função endotelial e rigidez vascular foram comparados entre usuários e não-usuários de estatina. Os dados estão apresentados como mediana (intervalo interquartil). Os resultados principais mostraram que o grupo benazepril apresentou menor proteína C reativa [0,38 (0,15-0,95) mg/dl vs 0,42 (0,26-0,59) mg/dl, p=0,020]. Houve, ainda, uma leve melhora da dilatação mediada por fluxo da artéria braquial no grupo benazepril (aumento 45%, p=0,057) em comparação com o grupo losartana (aumento 19%, p=0,132). Não houve diferença na velocidade da onda de pulso [8,5 (7,8-9,4) m/s vs 8,5 (7,0-9,7) m/s, p=0,280] e na pressão aórtica sistólica [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0,934] entre os grupos benazepril e losartana...

In hypertensive diabetic patients, the renin-angiotensin-aldosterone system is related to endothelial dysfunction, vascular stiffness and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are two of the most important medications that inhibit this system. Most international guidelines recommend them interchangeably, albeit small differences may have clinical relevance. The main objective was to compare inflammatory parameters (by C-reactive protein), endothelial function (by flow-mediated vasodilation) and vascular stiffness (by pulse wave velocity and aortic pressures) between benazepril and losartan in hypertensive diabetic patients whose blood pressure was not controlled by amlodipine. The secondary objective was a post-hoc analysis to study possible synergism between statins and renin-angiotensin-aldosterone system inhibitors. Blood pressure reduction, endothelial function and vascular stiffness were compared between patients using or not statins. Main results showed that C-reactive protein had lower values in benazepril group [0.38 (0.15-0.95) mg/dl vs 0.42 (0.26-0.59) mg/dl, p=0.020]. There was a slightly higher flow-mediated vasodilation response in benazepril group (45% of increase, p=0.057) than in losartan group (19% of increase, p=0.132). Aortic systolic blood pressure [129 (121-145) mmHg vs 123 (117-130) mmHg, p=0.934] and carotid-femoral pulse wave velocity [8.5 (7.8-9.4) m/s vs 8.5 (7.0-9.7) m/s, p=0.280] were the same between groups. Secondary results showed that patients using statins had greater reduction in mean systolic blood pressure in 24 hour monitoring [134 (120-146) mmHg to 122 (114-135) mmHg, p=0.007] than patients not using statins [137 (122-149) mmHg to 128 (122-140) mmHg, p=0.362]. Patients using statins had higher flow-mediated vasodilation response [6.5% (5.1-7.1) to 10.9% (7.3-12.2), p=0.003] than those not using statins [7.5% (6.0-10.2) to 8.3% (7.5-9.9), p=0.820]...

The effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate of amlodipine besylate, using the rotating disk method

The aim of this study was to evaluate the effect of dissolution medium, rotation speed and compaction pressure on the intrinsic dissolution rate (IDR) of the antihypertensive drug amlodipine besylate, using the rotating disk method. Accordingly, a fractional factorial design (33-1) was used, employing dissolution media (water, phosphate buffer pH 6.8 and HCl 0.1 M), rotation speed (50, 75 and 100 rpm), and compaction pressure (1000, 1500 and 2000 psi) as independent variables. The assays were randomized and statistically compared using the Statistica(r) 11 software program. Significance testing (ANOVA) indicated that the dissolution medium had a considerable impact on the IDR of amlodipine besylate. Analysis of the linear and quadratic components of the variables led to the proposition of a mathematical model that describes the IDR as a function of the parameters studied. Conversely, the levels of compaction pressure and rotation speed employed during experimental planning were less relevant, especially when the assay was conducted in the HCl 0.1 M medium.

A finalidade do presente trabalho foi avaliar o efeito do meio de dissolução, velocidade de rotação e pressão de compactação na velocidade de dissolução intrínseca (VDI) do fármaco anti-hipertensivo besilato de anlodipino, usando o método do disco rotativo. Dessa forma, foi utilizado um planejamento experimental do tipo fatorial facionado (33-1) utilizando como variáveis independentes o meio de dissolução (água, HCl 0,1M e tampão fosfato pH 6,8), velocidade de rotação (50, 75 e 100 rpm) e pressão de compactação do fármaco (1000, 1500 e 2000 psi). Os ensaios foram randomizados e comparados estatisticamente pelo software Statistica(r) 11. A análise de variância (ANOVA) indicou que o meio de dissolução exerce considerável impacto na VDI do besilato de anlodipino. A análise das variáveis em seus componentes lineares e quadráticos permitiu a proposição de um modelo matemático que descreve a VDI em função dos parâmetros estudados. Por outro lado, os níveis de pressão de compactação e velocidade de rotação empregados exercem efeito menos relevantes, especialmente quando o ensaio é conduzido em HCl 0,1 M.

Avaliação comparativa em longo prazo da eficácia, tolerabilidade e efeitos metabólicos de combinações de atenolol com anlodipino ou clortalidona no tratamento da hipertensão arterial ? subanálise do estudo ATENAS / Comparative evaluation in the long range of the efficacy, tolerability and metabolic effects of combinations of atenolol with amlodipine or chlorthalidone in the treatment of hypertension ? sub-analysis of ATENAS study

Em estudo multicêntrico, aberto, randomizado e comparativo (estudo ATENAS) foi avaliado no período de extensão (da 12ª a 48ª semanas) a eficácia anti-hipertensiva, a tolerabilidade, a segurança e o impacto sobre a sensibilidade à insulina da combinação galênica única de atenolol 25 a 50 mg e anlodipino 5 mg comparada à combinação livre de atenolol 50 a 100 mg com clortalidona 12,5 a 25 mg em hipertensos primários estágios 1 e 2. Observamos que a combinação de atenolol e anlodipino é segura, bem tolerada e proporciona em longo prazo maiores reduções da pressão arterial que o tratamento com a combinação de atenolol e clortalidona. A maior redução da pressão arterial permitiu que maior percentual de pacientes tivesse a pressão arterial controlada tanto para o critério de PAD < 90 mmHg (87,7% a 95,9%) quanto para PAD £ 85 mmHg (69,9% a 90,2%). Menor incidência de bradicardia, cefaleia, alterações lipídicas e glicêmicas foram relatadas nos pacientes tratados com a combinação de atenolol e anlodipino. A incidência de edema de membros inferiores neste grupo (6,1%) foi menor que a relatada na literatura para mesma dose de anlodipino em monoterapia. O tratamento com atenolol combinado com o anlodipino não alterou a sensibilidade à insulina. Concluindo, a combinação em formulação galênica única de atenolol e anlodipino em doses baixas a medianas constitui boa opção terapêutica da hipertensão arterial primária estágio 1 e 2 em longo prazo, é superior à combinação de atenolol e clortalidona, sendo opção preferencial para pacientes hipertensos com doença arterial coronariana.

Saúde da família e utilização de medicamentos anti-hipertensivos e antidiabéticos / Family health and antihypertensive and antidiabetic drug use

Fundamentos: O acesso e a utilização dos medicamentos de uso contínuo assumem grande importância notratamento da hipertensão arterial e do diabetes mellitus. Objetivo: Analisar o perfil de utilização dos medicamentos para controle de hipertensão arterial e/ou diabetes mellitus e o local de aquisição, por adultos residentes na área de abrangência de uma Unidade Saúde da Família de Ponta Grossa (PR), entre 2006 e 2007. Métodos: Estudo transversal. A seleção dos sujeitos realizou-se por amostragem sistemática. Foram entrevistadas 374 pessoas. O período recordatório utilizado foi de 7 dias. Realizou-se análise estatística descritiva com utilização de frequência absoluta e relativa. Resultados: A prevalência referida de hipertensão arterial e diabetes mellitus foi 22,2% e 8%, respectivamente. Eram hipertensos 70% dos diabéticos. Dos entrevistados que se diziam hipertensos, 66,3% utilizavam medicamentos anti-hipertensivos. Entre os diabéticos, 70% fazia uso de antidiabéticos. A terapêutica anti-hipertensiva combinadamais frequente foi entre diuréticos e inibidores da enzima conversora de angiotensina (47,2%). Verificou-se que12,5% dos entrevistados que utilizavam anti-inflamatório não esteroidal consumiam concomitantemente antihipertensivos. Apenas 7,1% dos diabéticos entrevistados relataram utilizar insulina. Quanto ao local de aquisição desses medicamentos, 54,7% foram obtidos em unidades básicas de saúde. Mais da metade dos betabloqueadores e diuréticos precisaram ser comprados, mesmo sendo medicamentos que fazem parte da Relação Nacional de Medicamentos. Conclusão: Apesar dos avanços do SUS, os medicamentos essenciais, por vezes, não estão disponíveis nas Unidades Saúde da Família aos portadores de hipertensão arterial e diabetes mellitus.

Background: Accessing and taking prescription drugs for ongoing use is of great importance for the management of hypertension and diabetes mellitus. Objective: To assess the use of drugs for controlling hypertension and/or diabetes mellitus and examine where these drugs are acquired among adults living in the area covered by a Family Health Center in the town of Ponta Grossa, southern Brazil, in 2006 and 2007. Methods: Through a cross-sectional study with asystematic sampling approach, 374 people were interviewed with a recall period of seven days, followed by a descriptive statistical analysis ofabsolute and relative frequency. Results: The reported prevalence of hypertension and diabetes mellitus reached 22.2% and 8% respectively, with 70% of the diabetic respondents presenting highblood pressure. Among those reporting hypertension, 66.3% took antihypertensive drugs. Among thediabetics, 70% reported antidiabetic drug use. The combined antihypertensive drug therapy mostcommonly included diuretics and angiotensinconverting enzyme inhibitors (47.2%), with 12.5% of the respondents reporting nonsteroidal antiinflammatory drug use concomitantly with antihypertensive drugs. Only 7.1% of the diabetic respondents reported insulin use. Drugs were acquired mainly (54.7%) from basic health units. Morethan 50% of the beta-blockers and diuretics had to be purchased, although appearing on the National List of Essential Medicines. Conclusion: Despite advances in Brazil’s National Health System, essential drugs are not always able at Family Health Centers to patients with hypertension and diabetes mellitus.

Perfil da terapêutica utilizada em pacientes hipertensos atendidos em hospital público / Profile of therapy used in hypertensive patients treated at the public hospital

JUSTIFICATIVA E OBJETIVOS: Estudos evidenciam ser fundamentais o controle e o tratamento da hipertensão, a fim de reduzir eventos cardiovasculares. Estima-se que aproximadamente 30 milhões de brasileiros são atingidos pela doença. O objetivo deste estudo foi analisar o perfil da terapêutica utilizada em pacientes hipertensos em hospital público, bem como identificar as principais comorbidades associadas conforme o sexo. MÉTODO: Trata-se de um estudo descritivo, retrospectivo, através da análise de prontuários de pacientes atendidos no períodode maio a julho de 2010 no Ambulatório de Cardiologia no Hospital de Urgências de Goiânia (HUGO). Foi utilizada média e desvio-padrão para planificação dos dados e posteriormente foram tratados estatisticamente. RESULTADOS: Foram analisados 103 prontuários de pacientes com média de idade de 59,41 ± 14,12 anos, sendo 52% do sexo feminino. As principais comorbidades associadas ao sexo feminino foram dislipidemia (20%), diabetes mellitus e neoplasia (16%).Em contrapartida no sexo masculino foram dislipidemia (25%), doença de Chagas (18%) e neoplasias (16%), porém não houve diferença significativa. A hipertensão arterial sistêmica (HAS) pode ter sido responsável pelo aparecimento de 49 (48%) dos casos diagnosticados de doença arterial coronariana (DAC), insuficiência cardíaca (IC) e acidente vascular encefálico (AVE), durante o tratamento de HAS (p < 0, 032). A terapêutica mais utilizada para o tratamento da HAS neste estudo foi a associação de três ou mais medicamentos, sendo os diuréticos (26%), inibidores da enzima conversora de angiotensina II (IECA) 29% e os inibidores adrenérgicos(22%) os mais prescritos na terapia anti-hipertensiva. CONCLUSÃO: A terapêutica mais efetiva continua sendo a prevenção,estar atento aos fatores de risco e buscar sempre a adesão do paciente ao tratamento.

BACKGROUND AND OBJECTIVES: Studies show that it is essential to control and treatment of hypertension in order to reduce cardiovascular events. It is estimated that approximately 30 million Brazilians are afflicted by disease. The aim of this study was to analyze the profile of the therapy used in hypertensive patients in a public hospital, as well as identify key comorbidities by gender. METHOD: This is a descriptive retrospective study, by analyzing medical records of patients treated between May to July 2010 the Cardiology Outpatient Clinic at Hospital de Goiânia (HUGO). We used mean and standard deviation of data for planning and subsequently were treated statistically.RESULTS: We analyzed medical records of 103 patients with mean age 59.41 ± 14.12 years, 52% female. The main comorbidities associated female were dyslipidemia (20%), diabetes mellitusand neoplasm's (16%). In contrast in males were dyslipidemia(25%), Chagas disease (18%) and neoplasm's (16%), but differences were not significant. Hypertension may have been responsiblefor the appearance of 49 (48%) of diagnosed cases of coronary artery disease (CAD), heart failure (CHF) and cerebrovascular accident (CVA) during treatment of hypertension (p < 0, 032). The most commonly used therapy for thetreatment of hypertension in this study was the association oft hree or more medications, diuretics (26%), inhibitors of angiotensin converting enzyme (ACEI) 29% and adrenergic inhibitors(22%) were prescribed on antihypertensive therapy. CONCLUSION: A more effective therapy is the prevention, bea ware of the risk factors and to always seek the patient's adherence to treatment.

HPLC method development for the simultaneous analysis of amlodipine and valsartan in combined dosage forms and in vitro dissolution studies

A simple, rapid and reproducible HPLC method was developed for the simultaneous determination of amlodipine and valsartan in their combined dosage forms, and for drug dissolution studies. A C18 column (ODS 2, 10 μm, 200 x 4.6 mm) and a mobile phase of phosphate buffer (pH 3.6 , 0.01 mol L-1):acetonitrile: methanol (46:44:10 v/v/v) mixture were used for separation and quantification. Analyses were run at a flow-rate of 1 mL min-1 and at ambient temperature. The injection volume was 20 μL and the ultraviolet detector was set at 240 nm. Under these conditions, amlodipine and valsartan were eluted at 7.1 min and 3.4 min, respectively. Total run time was shorter than 9 min. The developed method was validated according to the literature and found to be linear within the range 0.1 - 50 μg mL-1 for amlodipine, and 0.05 - 50 μg mL-1 for valsartan. The developed method was applied successfully for quality control assay of amlodipine and valsartan in their combination drug product and in vitro dissolution studies.

Desenvolveu-se método de HPLC rápido e reprodutível para a determinação simultânea de anlodipino e valsartana em suas formas de associação e para os estudos de dissolução dos fármacos. Utilizaram-se coluna C18 (ODS 2, 10 μm, 200 x 4,6 mm) e fase móvel tampão fosfato (pH 3,6, 0,01 mol L-1):acetonitrila: metanol para a separação e a quantificação. As análises foram efetuadas com velocidade de fluxo de 1 mL min-1 e à temparatura ambiente O volume de injeção foi de 20 μL e utilizou-se detector de ultravioleta a 240 nm. Sob essas condições, anlodipino e valsartana foram eluídas a 7,1 min e 3,4 min, respectivamente. O tempo total de corrida foi menor que 9 min. O método desenvolvido foi validado de acordo com a literatura e se mostrou linear na faixa de 0,1-50 μg mL-1 para anlodipino e de 0,05-50 μg mL-1 para valsartana. O método desenvolvido foi aplicado com sucesso para ensaios de controle de qualidade de associações de anlodipino e valsartana e nos estudos de dissolução in vitro.

Efeitos do ramipril, captopril e sinvastatina na injúria da preservação a frio de rins de ratos / Effects of ramipril, captopril, and simvastatin on cold-storage damage in rat kidneys

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...

Hypotensive action of an aqueous extract of Pimenta dioica (Myrtaceae) in rats

The intra-venous (i.v.) hypotensive action of the final aqueous fraction of Pimenta dioica was studied in Spontaneously Hypertensive Rats (SHR). The rats were anaesthetized (sodium pentobarbital 50 mg/kg), the trachea, right carotid artery and jugular vein were cannuated for adequate ventilation, direct blood pressure measurement and intra-venous administration of extract, solutions and drugs. The arterial line was connected to a pressure transducer (Viggo-Spectramed model P23 XL) and a polygraph (Grass model 7H) and monitored continuously during the firts five minutes after plan extract administration and then at 5 and 15 minute intervals for one hour. Responses were taken as the maximum pressure changes observed during this period. Increasing doses of the final aqueous fraction were given i.v. to groups of six SHR each. It produced a dose dependent decrease in blood pressure and the ED50 was 45 mg/kg. To discard that the hypotensive effect of the extracts was due to its ionic composition, a solution containing KCl, NaCl, CaCl2 adn MgCl2 equivalent to hte ion contents present in a dose of 50mg/kg of total asqueous extract was injected to Sprague-Dawley rats (SDN) using the same method as described above. It did not produce singificant changes in blood pressure. Pharmacological antagonistic studies were done injection either autonomic ganglion,alfa adrenoceptor,beta adrenoceptor and cholinergic receptor blockers prior to extract administration in SHR rats. Atropine, propranolol and phentolamine did no affect the hypotensive effect to the final aqueous fraction. With hexamethonium (autonomic ganglion blocker) the hypotensive response was diminished in a significant way (p<0.05). The hypotensive action of the final aqueous extract was not mediated through cholinergic, alfa o beta adrenergic receptors. The extract may posses vasorelaxing activity which could no be eviden after autonomic ganglion blockade due to extreme vasodilation present prior to extract administration. Future studies should address the question of a possible direct vasodilating effect of the extracts. Key words: Pimenta dioica, traditional medicine, herbal medicine, antihypertensive effect, arterial hypertension