Correspondência de teor de dissulfeto de captopril com odor de enxofre em comprimidos de captopril 25 mg, provenientes de farmácias públicas (postos de saúde) e drogarias comerciais / Correspondence of captopril disulfide content with sulfur odor in 25 mg captopril tablets from public pharmacies (health clinics) and commercial drugstores

Introdução: O captopril (CP) é o medicamento de escolha para o tratamento da hipertensão arterial. Sua degradação leva à formação do dímero dissulfeto de captopril (DSCP), este associado a um odor forte no medicamento, podendo causar abandono do tratamento pelo paciente. Objetivo: Determinar DCSP, associar a percepção olfativa de odor de enxofre desprendido do produto e realizar a avaliação de bula de comprimidos de captopril 25 mg distribuídos pelos setores público e privado. Método: Foi verificado o desempenho do método de determinação do CP e DSCP pela Farmacopeia Brasileira 6a ed. por HPLC (DAD). Foram analisados 13 produtos de comprimidos de captopril 25 mg, sendo dois provenientes do setor público de lotes diferentes e mesmo fabricante e 11 do setor privado de diferentes fabricantes e lotes. Foram avaliados aspectos do comprimido quanto à percepção de odor, determinação de peso, identificação e teor de CP e de DSCP e análise do conteúdo da bula. Resultados: Dentre os 13, o medicamento vencido apresentou 4,4% de DSCP, os demais estavam de acordo com a especificação. Verificouse  correspondência do odor de enxofre perceptível com teor de DSCP acima de 0,5%. Considerando os textos de bula sobre odor de enxofre, as constatações foram: nenhuma informação (três produtos), odor característico (dois), leve odor de enxofre (um), leve odor de enxofre sem diminuir a eficácia (sete). Conclusões: As amostras apresentaram resultados satisfatórios para os ensaios realizados. Verificou-se falta de homogeneidade nas informações das bulas sobre o odor dos comprimidos. A percepção do paciente quanto ao odor de enxofre, mesmo dentro do limite tolerado de DSCP, pode levar a não aceitação do medicamento e consequente não adesão ao tratamento da hipertensão, além de gerar prejuízos ao SUS.

Introduction: Captopril (CP) is the drug of choice for the treatment of hypertension. Its degradation leads to the formation of captopril disulfide dimer (DSCP), associated with a strong odor in the drug, which can cause the patient abandonment of treatment. Objective: To determine DCSP, associate the olfactory perception of the sulfur odor given off by the product and carry out the evaluation of the package insert for captopril 25 mg tablets distributed in the public and private sectors. Method: The performance of CP and DSCP determination method of the Brazilian Pharmacopoeia 6 ed was verified by HPLC (DAD). Thirteen products of 25 mg captopril tablets were analyzed, 2 of which came from the public sector from different batches and the same manufacturer: the other 11 came from the private sector from different batches and manufacturers. The samples were analyzed regarding appearance, odor perception, identification, weight determination, CP and DSCP content (by HPLC) and package insert content. Results: Among the 13, the expired drug had 4.4% DSCP; the others were in accordance with the specification. Correspondence of perceptible sulfur odor was established for drugs with DSCP content above 0.5%. Considering the texts on sulfur odor in the package inserts, the findings were: none information (3 products), characteristic odor (2), slight sulfur odor (1), slight sulfur odor without decreasing effectiveness (7). Conclusions: The samples showed satisfactory results for the tests performed. There was a lack of homogeneity in the information in the package inserts about odor of the tablets. The patient's perception of sulfur odor, even within the tolerated limit of DSCP, can lead to non-acceptance of the drug and consequent non- adherence to the treatment of hypertension, in addition to causing damage to the SUS.

Potential of green and roasted coffee beans and spent coffee grounds to provide bioactive peptides.

Protein extracts from green and roasted coffee beans and from spent coffee grounds (SCG) were evaluated as bioactive peptides sources. The in silico approach revealed a high frequency of the occurrence (A) of dipeptidyl peptidase-IV (DPP-IV) (0.62) and angiotensin I-converting enzyme (ACE) inhibitor peptides (0.44) in the 11S coffee globulin, which could be released after digestion. After in vitro digestion of the protein, the green bean and SCG proteins were more susceptible to proteolysis, releasing smaller polypeptides (3.4 kDa), which showed higher anti-hypertensive potentials (IC50 = 0.30 and 0.27 mg soluble protein/mL). However, the antioxidant capacity only increased for the roasted coffee and SCG extracts due to antioxidant groups formed during roasting. The heat treatment applied during coffee brewing increased the sensitivity of the SCG extract to proteolysis, leading to their high anti-hypertensive and antioxidant potentials. Therefore, the 11S coffee globulin is a precursor of a series of bioactive peptides.

Structural and molecular bases of angiotensin-converting enzyme inhibition by bovine casein-derived peptides: an in silico molecular dynamics approach.

The angiotensin-converting enzyme (ACE) plays a key role in blood pressure regulation process, and its inhibition is one of the main drug targets for the treatment of hypertension. Though various peptides from milk proteins are well-known for their ACE-inhibitory capacity, research devoted to understand the molecular bases of such property remain scarce, specifically for such peptides. Therefore, in this work, computational molecular docking and molecular dynamics calculations were performed to enlighten the intermolecular interactions involved in ACE inhibition by six different casein-derived peptides (FFVAPFPEVFGK, FALPQYLK, ALNEINQFYQK, YLGYLEQLLR, HQGLPQEVLNENLLR and NAVPITPTLNR). Two top ranked docking poses for each peptide (one with N- and the other C-terminal peptide extremity oriented towards the ACE active site) were selected for dynamic simulations (50 ns; GROMOS53A6 force field), and the results were correlated to in vitro ACE inhibition capacity. Two molecular features appeared to be essential for peptides to present high ACE inhibition capacity in vitro: i) to interact with the S1 active site residues (Ala354, Glu384, and Tyr523) by hydrogen bonds; ii) to interact with Zn2+ coordinated residues (His383, His387, and Glu411) by short-lenght hydrogen bonds, as observed in the cases of ALNEINQFYQK (IACE = 80.7%), NAVPITPTLNR (IACE = 80.7%), and FALPQYLK (IACE = 79.0%). Regardless of the temporal stability of these strong interactions, they promoted some disruption of Zn2+ tetrahedral coordination during the molecular dynamics trajectories, and were pointed as the main reason for the greatest ACE inhibition by these peptides. On the other hand, peptides with intermediate inhibition capacity (50% < IACE < 45%) interacted mainly by weaker interactions (e.g.: electrostatic and hydrophobic) with the Zn2+ coordinated residues, and were not able to change significantly its tetrahedral coordination structure. These findings may: i) assist the discrimination in silico of "good" and "bad" ACE-inhibitory peptides from other food sources, and/or ii) aid in designing de novo new molecules with ACE-inhibitory capacity. Communicated by Ramaswamy Sarma.

Facts and reflections on COVID-19 and anti-hypertensives drugs.

Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.

Effect of Early Normotension with Olmesartan on Rho-kinase Activity in Hypertensive Patients.

BACKGROUND: Angiotensin II is a potent activator of the Rho-kinase (ROCK) pathway, through which it exerts some of its adverse vasoconstrictor effects. Clinical evidence on the effects of blocking the angiotensin II receptor 1 on ROCK activity in hypertensive patients is scarce. OBJECTIVE: To demonstrate that ROCK activity in peripheral blood mononuclear cells (PMBCs) in patients with essential hypertension is reduced earlier than previously observed, along with blood pressure (BP) lowering on treatment with olmesartan. METHODS: Prospective pilot open study; 17 hypertensive patients were treated with progressive olmesartan doses starting with 20 mg qd. BP was measured at 3, 6 and 9 weeks after treatment initiation. If treatment failed to normalize BP after 3 weeks, olmesartan dose was increased to 40 mg qd, and if still hypertensive after 6 weeks, 12.5 mg of hydrochlorothiazide qd was added. ROCK activity was measured at baseline and 9 weeks after treatment as myosin phosphatase target subunit 1 phosphorylation (MYPT1-p/T ratio) in PBMC. RESULTS: Mean baseline BP was 162 ± 4.9/101 ± 2.4 mmHg. After 9 weeks of treatment, both systolic and diastolic BP were reduced by 41 and 22 mmHg, respectively (p<0.05). Mean pretreatment MYPT1- p/T ratio in PMBCs was significantly reduced by 80% after 9 weeks with olmesartan (p<0.01). CONCLUSION: Normotension achieved after 9 weeks in 82% of the patients treated with olmesartan was associated with a significant reduction of ROCK activity in PBMC.

[Principal conclusions of the Argentine Consensus on Arterial Hypertension]. / Principales conclusiones del Consenso Argentino de Hipertensión Arterial.

A summary is presented in this article of the principal concepts of the Argentine Consensus on Arterial Hypertension, which has been carried out for the first time jointly by the three main scientific societies associated with the diagnosis and treatment of arterial hypertension in Argentina (Argentine Society of Arterial Hypertension, Argentine Society of Cardiology and Argentine Federation of Cardiology). Among its main points, is emphasised the need to improve the diagnosis and control of high blood pressure, the use of ambulatory blood pressure measurement techniques, the importance of the risk stratification of the hypertensive patient, and the early use of pharmacological combinations in the treatment as a means to quickly achieve control. Finally, it lists the main recommendations for the management of hypertension in special populations, such as pregnant women, elderly people, diabetics, resistant patients, as well as patients with chronic kidney disease.

Control of Blood Pressure and Cardiovascular Outcomes in Type 2 Diabetes.

High blood pressure in patients with diabetes mellitus results in a significant increase in the risk of cardiovascular events and mortality. The current evidence regarding the impact of intervention on blood pressure levels (in accordance with a specific threshold) is not particularly robust. Blood pressure control is more difficult to achieve in patients with diabetes than in non-diabetic patients, and requires using combination therapy in most patients. Different management guidelines recommend initiating pharmacological therapy with values >140/90 mm/Hg; however, an optimal cut point for this population has not been established. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90mmHg, and that values approaching 130/80mmHg should be recommended. Initial treatment of hypertension in diabetes should include drug classes demonstrated to reduce cardiovascular events; i.e., angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, diuretics, or dihydropyridine calcium channel blockers. The start of therapy must be individualized in accordance with the patient's baseline characteristics, and factors such as associated comorbidities, race, and age, inter alia.

Management of Hypertension and High Low-Density Lipoprotein in Pediatric Type 1 Diabetes.

OBJECTIVE: To evaluate hypertension and hyperlipidemia management patterns in youth with type 1 diabetes and to assess perceived effectiveness of management strategies and barriers to management. STUDY DESIGN: An electronic survey, including clinical scenarios, fielded to pediatric providers (members of the American Diabetes Association Diabetes in Youth Interest Group, Pediatric Endocrine Society, or T1D Exchange). RESULTS: Respondents (N = 207, 86% MDs, 68% female) were practicing clinicians for youth with type 1 diabetes. As an initial recommendation, the overwhelming majority of respondents (83%-99%) endorsed lifestyle and nonmedical recommendations (eg, improve glycemic control) for hypertension and hyperlipidemia. Yet, few (6%-17%) reported these recommendations as effective. Many respondents (57%) reported referring to another specialist for hypertension, whereas few (8%) reported referring to another specialist for hyperlipidemia management. Approximately one-fifth (21%) of respondents never initiate antihypertensive medications, whereas only 8% never initiate lipid-lowering medication. Among prescribers, the majority of respondents only started antihypertensive or lipid-lowering medications after persistent elevations and in the setting of either ineffective lifestyle or nonmedical interventions or additional cardiovascular risk factors. More than two-thirds of respondents endorsed medications as often effective for hypertension and hyperlipidemia (68% and 69%, respectively). CONCLUSIONS: Pediatric diabetes providers commonly defer prescribing antihypertensive and lipid-lowering medications until nonmedication interventions have been ineffective. Most providers describe medications, but not lifestyle interventions, as often effective. Efforts to align clinical practice with clinical guidelines are needed.

Echinodorus grandiflorus: Ethnobotanical, phytochemical and pharmacological overview of a medicinal plant used in Brazil.

Echinodorus grandiflorus (Cham. & Schltdl.) Micheli is a native Brazilian species used in traditional practices for the treatment of several conditions such as inflammatory diseases, arthritis and hypertension. Through a systematic review of the accumulated knowledge about the species E. grandiflorus, the botanical, phytochemistry, ethnobotanical and pharmacological properties of this medicinal plant demonstrates its potential to naturally provide anti-inflammatory and anti-oxidant with a special emphasis on anti-hypertensive and cardioprotective effects. The body of literature reports that the chemical composition of crude E. grandiflorus extracts are notably composed of diterpenoids and flavonoids metabolites. Pharmacological studies have shown that oral treatments using the hydroalcoholic extracts of leaves from this plant has a significant anti-inflammatory, anti-hypertensive, diuretic and cardioprotective effects in rats with no toxicity. The holistic activities of complex extracts are corroborated by the individuals mechanisms of action, as well as, synergistic benefits attributed to the isolated chemical major constituents in this species. In light of the serious health concerns ascribed, it is important to investigate medicinal plant species with histories of traditional use for circulatory problems to meet the growing demands by scientifically validating their use and safety.

Antihypertensive therapy increases natural immunity response in hypertensive patients.

AIMS: The aim of this work was to evaluate the effects of treatment of hypertension on the autoantibodies to apolipoprotein B-derived peptides (anti-ApoB-D peptide Abs) response, inflammation markers and vascular function. MAIN METHODS: Eighty-eight patients with hypertension (stage 1 or 2) were recruited and advised to receive perindopril (4mg), hydrochlorothiazide (25mg), or indapamide (1.5mg) for 12weeks in a blinded fashion. Office and 24-h ambulatory blood pressure monitoring (24h ABPM), flow-mediated dilatation (FMD), nitrate-induced dilatation (NID), titers of IgG and IgM anti-ApoB-D peptide Abs, hsCRP, and interleukins (IL-8 and IL-10) were evaluated at baseline and 12weeks after therapies. KEY FINDINGS: All treatments reduced office BP, and improved FMD (P<0.05 vs. baseline). The NID was improved only in the perindopril arm (P<0.05 vs. baseline). The 24h-ABPM was reduced with perindopril and hydrochlorothiazide therapies (P<0.05 vs. baseline), but not with indapamide, and this effect was followed by increase in titers of IgM Anti-ApoB-D peptide Abs (P<0.05 vs. baseline), without modifications in titers IgG Anti-ApoB-D peptide Abs and interleukins. Multivariable regression analysis has shown that change in the titers of IgM anti-ApoB-D peptide was associated with the changes in FMD (ß -0.347; P<0.05). SIGNIFICANCE: These findings shed light to a possible modulator effect of the antihypertensive therapy on the natural immunity responses and vascular function.

Hypotensive and diuretic effect of the butanolic soluble fraction of the hydroethanolic extract of bark of Scutia buxifolia Reissek in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Scutia buxifolia, a native tree popularly known as "coronilha", is widely used in Brazilian folk medicine for diuretic and anti-hypertensive purposes. AIM OF THE STUDY: We investigated the effects of a butanolic (BuOH) soluble fraction of the hydroethanolic extract (HESB) of bark of Scutia buxifolia on both blood pressure and urinary excretion of rats. The involvement of the nitric oxide/guanylate cyclase pathway in the hypotensive effect found was also explored. MATERIAL AND METHODS: We tested the effect of the BuOH soluble fraction of HESB on the mean arterial pressure (MAP) of anesthetized rats. The fraction was administered at doses of 1, 3 and 10mg/kg (i.v.) in normotensive rats during continuous infusion of vehicle (10 µl/min), or phenylephrine (4 µg/kg/min), or l-NAME (7 mg/kg/min), two approaches able to induce a sustained hypertensive state. In some experiments, a bolus injection of ODQ (2mg/kg) was administered in animals infused with phenylephrine before the administration of the BuOH soluble fraction of HESB. We also measured the effects of the BuOH soluble fraction on the MAP of spontaneously hypertensive rats (SHR). Separate groups of rats were treated orally with either HESB (10, 30 or 100mg/kg), or its BuOH soluble fraction (3, 10 or 30 mg/kg), and were subjected to measurement of diuresis and blood pressure. RESULTS: The BuOH soluble fraction of HESB (10mg/kg, i.v.) reduced the MAP of both phenylephrine-infused and SHR rats by 20.6 ± 6.0 and 41.8 ± 8.3 mm Hg, respectively. However, no hypotensive effect was found in normotensive animals infused with l-NAME, a non-selective inhibitor of nitric oxide synthase, or animals previously treated with the soluble guanylate cyclase inhibitor ODQ. The urinary excretion was increased by 70% at 6-8h after a single oral administration of the BuOH soluble fraction of HESB (10mg/kg), without change in urinary density, pH, or Na(+) and K(+) concentrations. In addition, MAP was lower 3h after the acute oral treatment with the BuOH soluble fraction (82.1 ± 3.8 mm Hg), compared with MAP of animals from the control group (97 ± 3.2 mm Hg). CONCLUSION: This study demonstrates that the BuOH soluble fraction of the hydroethanolic bark of Scutia buxifolia, which has its bark used in folk medicine for the treatment of hypertension mainly by its presumed diuretic properties, possesses both diuretic and hypotensive effects in rats, and that at least the hypotensive effect is fully dependent on activation of the nitric oxide/guanylate cyclase pathway.

Activation of angiotensin-(1-7)/Mas axis in the brain lowers blood pressure and attenuates cardiac remodeling in hypertensive transgenic (mRen2)27 rats.

Activation of the peripheral angiotensin-(1-7)/Mas axis of the renin-angiotensin system produces important cardioprotective actions, counterbalancing the deleterious actions of an overactivity of Ang II/AT1 axis. In the present study we evaluated whether the chronic increase in Ang-(1-7) levels in the brain could ameliorate cardiac disorders observed in transgenic (mRen2)27 hypertensive rats through actions on Mas receptor. Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats, instrumented with telemetry probe for arterial pressure (AP) measurement were subjected to 14 days of ICV infusion of Ang-(1-7) (200 ng/h) or Ang-(1-7) associated with Mas receptor antagonist (A779, 1 µg/h) or 0.9% sterile saline (0.5 µl/h) through osmotic mini-pumps. Ang-(1-7) infusion in (mRen2)27 rats reduced blood pressure, normalized the baroreflex control of HR, restored cardiac autonomic balance, reduced cardiac hypertrophy and pre-fibrotic alterations and decreased the altered imbalance of Ang II/Ang-(1-7) in the heart. In addition, there was an attenuation of the increased levels of atrial natriuretic peptide, brain natriuretic peptide, collagen I, fibronectin and TGF-ß in the heart of (mRen2)27 rats. Furthermore, most of these effects were mediated in the brain by Mas receptor, since were blocked by its selective antagonist, A779. These data indicate that increasing Ang-(1-7) levels in the brain can attenuate cardiovascular disorders observed in (mRen2)27 hypertensive rats, probably by improving the autonomic balance to the heart due to centrally-mediated actions on Mas receptor.

Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus.

In a recent work by our group involving a transcriptomics approach applied to the venom glands from Tityus stigmurus we identified a new family of peptides called Hypotensins (TSTI0006C) (Almeida et al., 2012). The cluster TSTI0006C was analyzed in the main 25 amino acid residues and named T. stigmurus Hypotensin (TistH), showing a molecular mass of 2.7 kDa, an absence of cysteines and the presence of two C-terminal proline residues, which are a bradykinin-potentiating peptide (BPP) signature. Here, we describe the homology modeling of the three-dimensional structure of TistH. In addition, we evaluated the cardiovascular effects elicited by TistH in normotensive rats. Firstly, TistH showed no cytotoxic effect on horse erythrocyte. Furthermore, in normotensive rats TistH was able to potentiate the hypotensive action of bradykinin (BK) and induced a vasorelaxant effect in mesenteric artery rings by endothelium-dependent release of nitric oxide (NO) and demonstrated independent inhibition of angiotensin converting enzyme (ACE). Our data can contribute to a better understanding of the structural and functional characteristics of TistH and suggest its potential use in cardiovascular diseases.

Estudio MULATA: muestra latinoamericana de pacientes con tensión arterial elevada / MULATA study: Latin American sample of high blood pressure patients

Introducción: Por prevalencia y trascendencia como factor de riesgo para enfermedad cardiovascular, la hipertensión arterial es una de las enfermedades de mayor importancia en la práctica médica. Este trabajo describe las características clínicas y sociodemográficas de una muestra de pacientes hipertensos con al menos un factor de riesgo cardiovascular adicional, en Argentina, Colombia y Venezuela. Metodología: Es un estudio de corte transversal, con recolección prospectiva de la información en una muestra por conveniencia de pacientes con hipertensión arterial que consultaron a los médicos participantes en cada uno de los tres países. Resultados: Se detectaron diferencias estadísticamente significativas en la distribución de los factores de riesgo cardiovascular (obesidad central, hipertensión arterial no controlada, tabaquismo y dislipidemia) entre las poblaciones de Colombia, Venezuela y Argentina. La población participante estuvo compuesta en su mayoría por mujeres (53,7%), la edad promedio fue de 59,3 +/- DE 13,6 años; 29% de los participantes en el estudio tenían cifras tensionales controladas en el momento de la evaluación. El manejo con dos medicamentos fue el más frecuente en la población total (40,6%) así como en los subgrupos, argentino (47,1%) y colombiano (46,4%), mientras que en la población venezolana el manejo más común fue monoterapia (45%). Los bloqueadores del sistema renina angiotensina II fueron los más utilizados en los tres países. Discusión: Los factores de riesgo cardiovascular susceptibles de ser modificados tienen diferencias geográficas que justifican cambios en su manejo. La hipertensión requiere no solamente manejo farmacológico, sino la intervención sobre estos factores.

Introduction: Due to its high prevalence and its importance as a risk factor for stroke, heart disease, and renal failure, hypertension is one of the most important diseases in common medical practice. The aim of this study was to describe the clinical and demographic characteristics of a sample of hypertensive patients, with at least one additional cardiovascular risk factor, in Argentina, Colombia and Venezuela. Methods: We performed a cross sectional study, with prospective data collection from a convenience sample of patients. Results: we found statistically significant differences in the distribution of cardiovascular risk factors (obesity, non-controlled hypertension, smoking and dyslipidemia) in the population of the different countries. There were slightly more women in our sample (53.7%), the average age was 59.3 (SD 13.6) years. In 29% of the patients hypertension was controlled. The most common practice in the whole sample was the use of two different drugs (40.6%). This was true both in Colombia (46.4%) and in Argentina (47.1%), while in Venezuela the use of monotherapy was more common (45%). Angiotensin II receptor antagonists are the most commonly used drug family in the three countries, either alone or in combination with other therapies. Discussion: Our population shows a poor control of blood pressure. Our patients need a more strict pharmacological therapy together with a strategy to identify and reduce all modifiable cardiovascular risk factors.

Pseudomelanosis duodeni associated with chronic renal failure.

Pseudomelanosis duodeni (PD) is a rare dark speckled appearance of the duodenum associated with gastrointestinal bleeding, hypertension, chronic heart failure, chronic renal failure and consumption of different drugs. We report four cases of PD associated with chronic renal failure admitted to the gastroenterology outpatient unit due to epigastric pain, nausea, melena and progressive reduction of hemoglobin index. Gastroduodenal endoscopy revealed erosions in the esophagus and stomach, with no active bleeding at the moment. In addition, the duodenal mucosa presented marked signs of melanosis; later confirmed by histopathological study. Even though PD is usually regarded as a benign condition, its pathogenesis and clinical significance is yet to be defined.

Hipertensão arterial sistêmica, microalbuminúria e terapia anti-hipertensiva / Systemic arterial hypertension, microalbuminuria and anti-hypertensive therapy

Objetivos: Verificar a prevalência de microalbuminúria em pacientes com hipertensão arterial sistêmica (HAS), relacionando-a com tipo de terapia, classes de drogas anti-hipertensivas e duração do tratamento.Métodos: Estudo observacional, descritivo, transversal, realizado de abril a setembro de 2006, com 153 hipertensos nos Ambulatórios de Clínica Médica e de Cardiologia do HU-UFSC, analisando variáveis como idade (geriátrico > 60 anos / não geriátrico < 60 anos), sexo, raça, duração do tratamento, nível de pressão arterial, fatores de risco cardiovasculares, tipos de terapia, classes de drogas anti-hipertensivas e excreção urinária de albumina.Resultados: A maioria dos pacientes era do sexo feminino (103/153 (67,3%)), da raça branca (134/153 (87,6%)), com proporção semelhante entre os grupos geriátrico e não geriátrico (51% e 49%, respectivamente), sendo a dislipidemia (111/153 (72,5%)) o fator de risco cardiovascular mais freqüente. A prevalência de microalbuminúria foi de 13,7% (21/153). A terapia dupla foi mais freqüente (70/153 (45,8%)), inclusive nos indivíduos com e sem microalbuminúria (13/21 (61,9%) e 57/132 (43,1%), respectivamente), seguida pela terapia tripla no primeiro grupo (4/21 (19,0%) e monoterapia no segundo (49/153 (37,1%)). Os anti-hipertensivos mais usados foram diuréticos tiazídicos (92/153 (60,1%)), inibidores da enzima conversora de angiotensina (87/153 (56,9%)) e beta-bloqueadores (59/153 (38,6%)), padrão observado no grupo com microalbuminúria (13/21 (61,9%), 10/21 (47,6%) e 9/21 (42,8%), respectivamente) e sem microalbuminúria (79/132 (59,8%), 77/132 (58,3%), 50/132 (37,8%)). Não houve relação entre duração do tratamento e presença de microalbuminúria.Conclusões: A prevalência de microalbuminúria foi de 13,7%. A freqüência de terapia com duas ou três classes de drogas foi proporcionalmente maior no grupo com microalbuminúria. As classes de drogas tiveram distribuição semelhante entre os dois grupos, exceto os IECA.

Treatment of essential hypertension does not normalize capillary rarefaction

OBJECTIVES: To determine if capillary rarefaction persists when hypertension is treated with angiotensin converting enzyme inhibitor, thiazidic diuretic and/or beta-blocker, and to identify which microcirculatory alterations (structural and functional) persist after anti-hypertensive treatment. METHODS: We evaluated 28 well-controlled essential hypertensive patients and 19 normotensive subjects. Nailfold videocapillaroscopy examination of the fourth finger of the left hand was used to determine the functional capillary densities at baseline, during post-occlusive hyperemia, and after venous congestion. Capillary loop diameters (afferent, apical and efferent) and red blood cell velocity were also quantified. RESULTS: Compared with normotensive subjects, hypertensive patients showed lower mean functional capillary density at baseline (25.1±1.4 vs. 33.9±1.9 cap/mm², p<0.01), during post-occlusive reactive hyperemia (29.3±1.9 vs. 38.2±2.2 cap/mm², p<0.01) and during venous congestion responses (31.4±1.9 vs. 41.1±2.3 cap/mm², p<0.01). Based on the density during venous congestion, the estimated structural capillary deficit was 25.1 percent. Mean capillary diameters were not different at the three local points, but red blood cell velocity at baseline was significantly lower in the hypertensive group (0.98±0.05 vs. 1.17±0.04 mm/s, p<0.05). CONCLUSIONS: Patients treated for essential hypertension showed microvascular rarefaction, regardless of the type of therapy used. In addition, the reduced red blood cell velocity associated with capillary rarefaction might reflect the increased systemic vascular resistance, which is a hallmark of hypertension.

Natural products inhibitors of the angiotensin converting enzyme (ACE): a review between 1980 - 2000 / Produtos naturais inibidores da enzima conversora de angiotensina (ECA): uma revisão entre 1980 - 2000

Inhibition of Angiotensin Converting Enzyme (ACE) is a modern therapeutic target in the treatment of hypertension. Within the enzyme cascade of the renin-angiotensin system, ACE removes histidyl-leucine from angiotensin I to form the physiologically active octapeptide angiotensin II, one of the most potent known vasoconstrictors. Therefore, a rationale for treating hypertension would be to administer drugs or natural compounds which selectively inhibit ACE. The present work constitutes a review of the literature of plants and chemically defined molecules from natural sources with in vitro anti-hypertensive potential based on the inhibition of ACE. The review refers to 321 plants, the parts utilized, type of extract and whether they are active or not. It includes also the names of 158 compounds isolated from higher plants, marine sponges and algae, fungi and snake venom. Some aspects of recent research with natural products directed to produce anti-hypertensive drugs are discussed. In this review, 148 references were cited.

A inibição da Enzima Conversora da Angiotensina (ECA) é um alvo terapêutico moderno e eficaz no tratamento da hipertensão arterial. Na cascata enzimática que envolve o sistema renina-angiotensina, a ECA promove a remoção dos aminoácidos histidil-leucina da angiotensina I para formar o octapeptídio angiotensina II, a qual é fisiologicamente ativa em diversos sistemas, e considerado como um dos mais potentes vasoconstrictores endógenos conhecido. Portanto, uma racionalidade no tratamento da hipertensão seria administrar drogas ou compostos de origem natural que inibam seletivamente a ECA. O presente estudo constitui uma revisão da literatura sobre plantas e moléculas de origem natural com potencial anti-hipertensivo, baseado na inibição in vitro da ECA. A revisão referencia 321 plantas, partes usadas, tipo de extrato e se é ativo ou não. Inclui ainda o nome de 158 compostos isolados de plantas superiores, esponjas e algas marinhas, fungos e venenos de cobra. Alguns aspectos de pesquisa recente com produtos naturais direcionados à produção de drogas anti-hipertensivas também são discutidos. Nesta revisão 148 referências foram consultadas.

Perfil do paciente hipertenso atendido em pronto-socorro: comparação com hipertensos em tratamento ambulatorial / Hypertensive patient´s profile seen in first-aid unit: comparison with hypertensives under ambulatory treatment

Os pacientes hipertensos muitas vezes não realizam o tratamento corretamente levando à falta de controle da doença e atendimentos em unidade de emergência. O objetivo deste estudo foi descrever e comparar o perfil de hipertensos atendidos em pronto socorro com aqueles seguidos em ambulatório quanto a características biossociais, hábitos de vida, conhecimento sobre a doença, tratamento e níveis de pressão arterial. Foram entrevistados 100 hipertensos atendidos no pronto socorro e 100 em acompanhamento ambulatorial no Hospital Universitário da Universidade de São Paulo (62% mulheres, 58 '+ OU -' 11 anos, 71% brancos, 64% com primeiro grau incompleto, 53% com ocupação manual não especializada, 53% com renda inferior a 5 salários mínimos e 53% não pertencentes à comunidade do hospital). Os hipertensos do pronto socorro foram significativamente diferentes (p<0,05) dos pacientes de ambulatório em relação a: pressão arterial mais elevada (174+27/109'+ OU -' 18 vs 143+20/88'+ OU -' 12 mm Hg); menor renda salarial; não pertencentes à comunidade do hospital (84% vs 23%); maior consumo de bebida alcoólica (92 vs 17 g de etanol/dia); descobriram ser hipertensos por sentir-se mal (60% vs 45%); mediam menos a pressão arterial (78% vs 96%); deixaram mais de tomar os remédios (44% vs 23%); e as mulheres usavam menos hormônio anticoncepcional (3% vs 16%). Os pacientes do ambulatório citaram mais dislipidemia (41%) como outros problemas de saúde, enquanto que para os do pronto socorro foram diabetes (42%), problemas cardíacos (19%) e hipertireoidismo (11%). O conhecimento sobre a doença e o tratamento não foi diferente entre os hipertensos do pronto socorro e ambulatório. Concluindo, as características desfavoráveis podem contribuir para que hipertensos não realizem tratamento anti-hipertensivo adequadamente, levando a atendimentos em unidades de emergência

Hypertensive patients dont't usually follow treatment appropriately, leading to diasease lack of control and assistance in first-aid units. The objective of this study describing hypertensives´profiles seen in first-aid units and comparing them with those who are seen in out-patient clinics regarding bio-social characteristics, life style, knowledge on the disease, and blood pressure treatment and levels. One-hundred hypertensives seen in the first-aid unit and 100 seen in the out-patient clinic of the School Hospital of the University of São Paulo were interviewed (62% women, 58'+ OR -'11 years, 71% white, 64% haven´t finished elementary school, 53% had non-specialized manual job, 53% had an income lower than US$419,45 monthly, and 53% did not belong to the hospital community). Hypertensives seen at the first-aid unit showed to be significantly different (p<0.05) from those seen at the out-patient clinic regarding: higher blood pressure (174'+ OR -'27/109'+ OR -'18 vs.143+20/88'+ OR -'12mmHg); lower income; not beloging to the hospital community (84% vs. 23%); greater alcohol intake (92 vs. 17g ethanol/day); got to know they were hypertensive because felt bad (60% vs. 45%); measured blood pressure less often (78% vs. 96%); did not take the medicine more often (44% vs. 23%); and the women use less anti-contraceptive hormone (3% vs. 16%). Patients seen at the out-patient clinic mentioned dyslipidemia more often (41%) as other health problems, whereas those seen at the out-patient clinic mentioned diabetes (42%), cardiac problems (19%), and hyperthyroidism (11%). The knowledge on the disease and treatment was not different between hypertensives seen at the first-aid unit and those seen at the out-patient clinic. In conclusion unfavorable characteristics can contribute to hypertensives do not follow anti-hypertension treatment adequately, leading to assistance in first-aid units

Estudo multicêntrico nacional para avaliação da eficácia e tolerabilidade da nifedipina oros em hipertensão arterial leve a moderada / Multicenter National Study for the evaluation of the efficacy and tolerance of nifedipine oral release osmotic system in mild to moderate hypertension

PURPOSE--Evaluation of the efficacy and tolerability of nifedipine oros in patients with mild to moderate essential hypertension without major target organ damage and the anti-hypertensive effect along the 24 hours. METHODS--Two hundred and three patients were studied. After two weeks placebo running period single dose of nifedipine oros (30 mg/day) was administered for 8 weeks. At the end of the 4th week, the non-responders (diastolic blood pressure > 90 mmHg or reduction in diastolic pressure < 10 mmHg), had the dosage increased to 60 mg/day. Laboratory tests and 24h blood pressure monitoring (60 patients) were performed at the beginning and at the end of the study. RESULTS--One hundred and ninety one patients completed the study. Fifty nine percent were considered responders at the end of the 4th week with nifedipine oros 30 mg/day and 41 needed dosage increment to 60 mg/day. At the end of the 8th week, all patients were considered responders to nifedipine oros. The blood pressure control extended throughout the 24h of the day. The most common adverse events were edema (14.6) and headache (12.4). Good and very good tolerability were informed by 85 of the patients. CONCLUSION--Nifedipine oros was able to control blood pressure efficaciously along the 24h period without important side effects. The possibility of once day dosage, increases the patient adherence to anti-hypertensive therapy.