Resistant and refractory hypertension: two sides of the same disease? / Hipertensão resistente e refratária: duas faces de uma mesma doença?

Abstract Refractory hypertension (RfH) is an extreme phenotype of resistant hypertension (RH), being considered an uncontrolled blood pressure besides the use of 5 or more antihypertensive medications, including a long-acting thiazide diuretic and a mineralocorticoid antagonist. RH is common, with 10-20% of the general hypertensives, and its associated with renin angiotensin aldosterone system hyperactivity and excess fluid retention. RfH comprises 5-8% of the RH and seems to be influenced by increased sympathetic activity. RH patients are older and more obese than general hypertensives. It is strongly associated with diabetes, obstructive sleep apnea, and hyperaldosteronism status. RfH is more frequent in women, younger patients and Afro-americans compared to RFs. Both are associated with increased albuminuria, left ventricular hypertrophy, chronic kidney diseases, stroke, and cardiovascular diseases. The magnitude of the white-coat effect seems to be higher among RH patients. Intensification of diuretic therapy is indicated in RH, while in RfH, therapy failure imposes new treatment alternatives such as the use of sympatholytic therapies. In conclusion, both RH and RfH constitute challenges in clinical practice and should be addressed as distinct clinical entities by trained professionals who are capable to identify comorbidities and provide specific, diversified, and individualized treatment.

Resumo A Hipertensão Arterial Refratária (HARf) representa um fenótipo extremo da hipertensão arterial resistente (HAR), sendo considerada a falência ao tratamento apesar do uso de 5 ou mais classes de anti-hipertensivos, incluindo um diurético tiazídico de longa ação e um antagonista mineralocorticoide. A HAR é comum (10-20%) entre os hipertensos em geral, sendo decorrente de hiperatividade do Sistema Renina Angiotensina Aldosterona e retenção hidrossalina. Aqueles com HARf correspondem a 5-8% dos resistentes e parecem sofrer maior influência catecolaminérgica. Os resistentes tendem a ter maior idade, ao sobrepeso e à obesidade. Comorbidades incluem diabetes, apneia obstrutiva do sono e status de hiperaldosteronismo. Refratários são afro-americanos em maior proporção, mais jovens e, predominantemente, mulheres. Ambos são fortemente associados à elevada albuminúria, HVE, doenças cardio e cerebrovasculares, além da doença renal crônica. O fenômeno do jaleco branco parece ser mais evidente nos resistentes. Quanto ao tratamento, a intensificação da terapia diurética está indicada nos resistentes, enquanto na HARf, a falência à terapia impôs novas alternativas de tratamento ("simpaticolíticas"). Em conclusão, tanto a HAR quanto a HARf constituem-se desafios na prática clínica e devem ser abordadas como entidades clínicas distintas por profissionais especialistas que identifiquem comorbidades e venham a prover um tratamento específico, diversificado e individualizado.

Diuretics are Similar to Losartan on Echocardiographic Target-Organ Damage in Stage I Hypertension. PREVER-Treatment Study / Diuréticos são Similares à Losartana na Avaliação Ecocardiográfica de Lesão a Órgãos-Alvo no Estágio I da Hipertensão. Estudo PREVER-Treatment

Abstract Blood pressure (BP)-lowering therapy improves left ventricular (LV) parameters of hypertensive target-organ damage in stage II hypertension, but whether there is a drug-class difference in echocardiographic parameters in stage I hypertension patients is less often studied. In the PREVER treatment study, where individuals with stage I hypertension were randomized for treatment with diuretics (chlorthalidone/amiloride) or losartan, 110 participants accepted to participate in a sub-study, where two-dimensional echocardiograms were performed at baseline and after 18 months of antihypertensive treatment. As in the general study, systolic BP reduction was similar with diuretics or with losartan. Echocardiographic parameters showed small but significant changes in both treatment groups, with a favorable LV remodeling with antihypertensive treatment for 18 months when target blood pressure was achieved either with chlorthalidone/amiloride or with losartan as the initial treatment strategy. In conclusion, even in stage I hypertension, blood pressure reduction is associated with improvement in echocardiographic parameters, either with diuretics or losartan as first-drug regimens.

Resumo A terapia de redução da pressão arterial (PA) melhora os parâmetros do ventrículo esquerdo (VE) na lesão a órgãos-alvo causada pela condição hipertensiva na hipertensão de estágio II; no entanto, se existem ou não diferenças relacionadas à classe de medicamentos nos parâmetros ecocardiográficos de pacientes com hipertensão estágio I é menos frequentemente estudado. No estudo PREVER-treatment, em que indivíduos com hipertensão estágio I foram randomizados para tratamento com diuréticos (clortalidona/amilorida) ou losartana, 110 participantes aceitaram participar de um subestudo, no qual foram realizados ecocardiogramas bidimensionais basais e após 18 meses de tratamento anti-hipertensivo. Como no estudo geral, a redução da PA sistólica foi semelhante com diuréticos ou com losartana. Os parâmetros ecocardiográficos mostraram pequenas mas significativas alterações em ambos os grupos de tratamento, com um remodelamento favorável do VE com tratamento anti-hipertensivo por 18 meses, quando a pressão arterial alvo foi atingida com clortalidona/amilorida ou com losartana como estratégia inicial de tratamento. Em conclusão, mesmo na hipertensão estágio I, a redução da pressão arterial está associada à melhora nos parâmetros ecocardiográficos tanto com o uso de diuréticos ou losartana como primeiro esquema de tratamento farmacológico.

Diuretic effect of alkaloids fraction extracted from Selaginella lepidophylla (Hook. et Grev.) Spring / Efecto diurético de la fracción con contenido de alcaloides extraída deSelaginella lepidophylla (Hook. et Grev.) Spring

The aerial parts of Selaginella lepidophylla (Hook. et Grev.) Spring, are used in Mexican folk medicine to treat renal diseases. The aim of this study was to measure the diuretic response of an aqueous extract (200 mg/kg) and alkaloids fraction at different doses (10, 40 y 100 mg/kg) of this plant and compare it with that induced by furosemide (4 mg/kg). Extract, alkaloids fraction, furosemide and vehicle were administered orally to adult rats and the effects in sodium, potassium and water balance were measured. The extract, the alkaloids fraction and the furosemide produced important and significant increments in urinary excretion of sodium, potassium and water with respect to control group. This increment was dose dependent of the alkaloids fraction, the highest dose produced a major effect. Potassium excretion increased but it was less than the one induced by furosemide. These results suggest that the aqueous extract and rich fraction in alkaloids from S. lepidophylla induce diuretic response.

Las partes aéreas de Selaginella lepidophylla (Hook. et Grev.) Spring, son usadas en la medicina tradicional mexicana para tratar enfermedades renales. El objetivo del estudio fue medir la respuesta diurética de un extracto acuoso (200 mg/kg) y de diferentes dosis de la fracción de alcaloides (10, 40 y 100 mg/kg) de esta planta y compararla con la inducida por furosemida (4 mg/kg). El extracto, la fracción de alcaloides, la furosemida y el vehículo fueron administrados por vía oral a ratas adultas y se midieron los efectos en el balance de sodio, potasio e hídrico. El extracto, la fracción de alcaloides y la furosemida produjeron importantes y significativos incrementos en la excreción urinaria de sodio, potasio y agua con respecto al grupo testigo. Este incremento fue dependiente de la dosis de la fracción de alcaloides, la dosis más alta produjo el mayor efecto. El incremento en la excreción de potasio fue menor al de furosemida. Los resultados sugieren que el extracto acuoso y la fracción rica en alcaloides de S. lepidophylla inducen una respuesta diurética.

Diuretic potential of aqueous extract of roots of Solanum xanthocarpum Schrad & Wendl, a preliminary study.

In traditional system of medicine S. xanthocarpum is used treating difficulty in urination and renal calculus. The objective of the present study was to scientifically evaluate diuretic potential of S. xanthocarpum. The study was divided into two phases of evaluation (acute and sub-acute) with administration of aqueous extract of S. xanthocarpum roots. The animals were treated with either aqueous extract of S. xanthocarpum (AqSX; 200, 400 mg/kg, po) or furosemide (25 mg/kg, po) or hydrochlorthiazide (HCTZ; 25 mg/kg, po). In acute study, the treated animals were observed for urine volume, urine pH, urine and serum electrolytes and creatinine after 6th and 24th h. While in sub-acute study observations for above mentioned parameters were done on day 1, day 7 and day 14. Diuretic index, natriuretic and saluretic potential were also calculated. The results indicated strong diuretic potential with AqSX (400 mg/kg). The diuretic prospective of AqSX was similar to furosemide without any type of toxicity based on the observations of serum electrolytes, serum creatinine and urine creatinine measurement. The findings support ethnobotanical use of S. xanthocarpum.

Efecto diurético agudo de los extractos etanólico y acuoso de Ceratopteris pteridoides (Hook) en ratas normales / Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats

Introducción. Ceratopteris pteridoides es un helecho semiacuático de la familia Parkeriacea, ampliamente utilizado en la medicina popular colombiana como diurético y colelitiásico, sobre el cual no existen reportes científicos que avalen su uso popular como diurético. Objetivo. Evaluar el efecto diurético agudo en dosis única y dosis repetidas a corto plazo, de los extractos etanólico y acuoso de C. pteridoides en un modelo in vivo . Materiales y métodos. El extracto etanólico total fue obtenido por maceración de la planta entera de C. pteridoides con etanol y el extracto acuoso fue obtenido por decocción a 60 °C por 15 minutos. Ambos extractos se sometieron a análisis fitoquímico preliminar y estudio histológico posterior a la administración de los extractos durante ocho días consecutivos (1.000 mg/kg). El efecto diurético se evaluó en ratas Wistar, tratadas con los extractos (500 mg/kg), en forma aguda y en dosis repetidas a corto plazo, cuantificando la eliminación de agua y la excreción renal de sodio y potasio por espectrofotometría de absorción atómica y, de cloruros, por titulación mercurimétrica. Resultados. En el modelo agudo, ambos extractos mostraron un significativo efecto diurético y de excreción renal de sodio y potasio en comparación con el control, mientras que con la administración en dosis repetidas a corto plazo mostraron efecto diurético sin eliminación de electrolitos. El estudio histopatológico no sugirió efectos tóxicos hepáticos o renales. Conclusión. Los resultados demuestran la actividad diurética de C. pteridoides y sustentan el uso popular dado a esta planta como diurético en la costa norte colombiana. Se requieren estudios posteriores que permitan aislar e identificar los compuestos responsables de la actividad y los mecanismos de acción involucrados.

Introduction. Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. Objective. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. Materials and methods. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. Results. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. Conclusion. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

In vivo and in vitro anti-natriuretic activity of twigs fraction from Dorstenia picta: a possible mechanism

The present study examine the in vivo effects of Dorstenia Picta [D. picta] on urinary volume and sodium excretion in streptozotocin-induced diabetic rats, and determine a possible mechanism by which the extract increased sodium transport in A6 cells monolayers. Administration of the plant extract at the dose of 150 mg/kg during two weeks decreased urinary volume and sodium excretion. In vitro study showed that, apical application of the plant extract at the dose of 100 micro g/mL does not significantly increase sodium transport, whereas basolateral administration provoked a significant [P<0.05] increase of sodium transport in a concentration-dependent manner. The plant extract increases the sodium transport by 69.93% versus 55.41% for insulin and 78.44% for adenosine after 30 min. Preincubation of A6 cells monolayers with inhibitor of all adenosine receptors completely suppressed adenosine and plant extract stimulated sodium transport. Interesting is that, the A1 inhibitor receptor [DPCPX], at 100 nM completely abolished the effect of plant extract. The plant extract increased sodium transport by increase PI3-kinase activity and this effect is strongly inhibited by LY-294002. These data also suggest that, the twigs methanol fraction from Dorstenia picta increase sodium transport via PI 3-kinase pathway and requires A1 adenosine receptor

Dissociação da resposta anti-hipertensiva e metabólica à losartana e espironolactona em ratos com síndrome metabólica experimental / Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome

INTRODUÇÃO: O tratamento da hipertensão arterial (HA) em indivíduos com síndrome metabólica (SM) é um desafio, uma vez que terapias não medicamentosas são de difícil implementação e o tratamento farmacológico ideal não está totalmente estabelecido. OBJETIVO: Avaliar o bloqueio do sistema renina angiotensina aldosterona (SRAA) na pressão arterial (PA), na função e na morfologia renais em modelo experimental de SM induzida por dieta hiperlipídica. MÉTODOS: Ratos Wistar receberam ração hiperlipídica a partir da quarta semana de vida, por 20 semanas. Os grupos tratados receberam Losartana ou Espironolactona a partir da oitava semana de vida. Avaliou-se semanalmente o peso corporal e a PA de cauda por pletismografia. Ao final do experimento, foram realizados testes de tolerância oral à glicose, perfil lipídico, clearance de creatinina, medida direta da PA, análise morfométrica renal. RESULTADOS: A administração de dieta hiperlipídica se associou ao desenvolvimento de SM, caracterizada por acúmulo central de gordura, hipertensão arterial, hiperglicemia e hipertrigliceridemia. Nesse modelo não foram observadas alterações da histomorfometria renal. O bloqueio do receptor AT1 da angiotensina II (Ang II) preveniu o desenvolvimento da HA. O bloqueio mineralocorticoide não apresentou eficácia anti-hipertensiva, porém, associou-se à redução da gordura abdominal. CONCLUSÃO: A dissociação da resposta anti-hipertensiva aos bloqueios dos receptores da Ang II e mineralocorticoide indica a participação da Ang II na gênese da HA associada à obesidade. A redução da obesidade central com a Espironolactona sugere a presença de efeito adipogênico mineralocorticoide.

INTRODUCTION: The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. OBJECTIVE: To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. METHODS: Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. RESULTS: The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. CONCLUSION: The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

pH salival, capacidad buffer, proteínas totales y flujo salival en pacientes hipertensos controlados usuarios de diuréticos / Salivary pH, buffer capacity, total proteins and salivary flow in controlled hypertensive patients diuretic users

La hipertensión arterial (HTA) es una enfermedad cardiovascular que padece gran parte de la población mundial y nacional, alcanzando en Chile un 26,9 por ciento en el año 2010. El objetivo fue determinar pH salival, capacidad buffer, proteínas totales y flujo salival, en pacientes hipertensos controlados usuarios de diuréticos. Se analizaron 14 muestras de saliva no estimulada de pacientes hipertensos controlados con diuréticos y 10 muestras de saliva no estimulada de personas que no padecían enfermedades sistémicas y no tomaban medicamentos, los valores obtenidos de pH salival, capacidad buffer, flujo salival y proteínas totales fueron determinados en ambos grupos. La mediana obtenida en las muestras de hipertensos controlados con diuréticos, para el pH salival fue de 6,83; para la capacidad buffer fue 4,86; para el flujo salival fue 0,55 ml/min y para las proteínas totales salivales fue de 1,09 g/dL. Para el grupo de pacientes sanos la mediana fue de 6,88 para el pH; 4,25 para la capacidad buffer; 1,8 ml/min para el flujo salival y 0,29 g/dL para las proteínas totales salivales. Además, no se encontró asociación entre el flujo salival (rs = 0,425), capacidad buffer (rs = 0,283) y concentración de proteínas (rs = 0,245) con la dosis del diurético (p > 0,05) . Se encontró que existieron diferencias estadísticamente significativas en el flujo salival y la concentración de proteínas salivales entre el grupo de pacientes hipertensos y de pacientes sanos (U Mann-Wthitney P < 0,005). No existían diferencias estadísticamente significativas de pH salival y capacidad buffer entre pacientes hipertensos controlados y pacientes sanos (U Mann-Wthitney P >0,005). Los pacientes que sufren HTA y están siendo controlados con diuréticos tienen una disminución del flujo salival y un aumento de la concentración de proteínas, no viéndose afectadas las variables de pH y capacidad buffer.

Introduction: Hypertension (HT) is a cardiovascular disease with a high prevalence around the world. In Chile at year 2010 it reached 26.9 percent of the population. Objective: To determine salivary pH, buffering capacity, total proteins and salivary flow in controlled hypertensive diuretic users and a group without systemic diseases. Methods: 14 samples of unstimulated saliva of patients with hypertension treated with diuretics and 10 samples of unstimulated saliva of people without systemic diseases and not taking medication were analyzed. pH, salivary buffering, salivary flow and total protein were determined in both groups. Results: The figures for the treated HT patients were as follows: pH: 6.83, buffer capacity: 4.86, salivary flow: 0.55 ml / min and total salivary proteins: 1.09 g / dL. For those without systemic diseases the results were: pH: 6,88, buffer capacity: 4,25, saliva flow: 1.8 ml / min and total salivary protein: 0.29 g / dL. No association was found between salivary flow (rs = 0.425), buffering capacity (rs = 0.283) and protein concentration (rs = 0.245) with the diuretic dose (p > 0.05). Statistically significant differences were found in salivary flow and total salivary protein concentration between the group with hypertension and without. (U Mann-Wthitney P > 0.005). No statistically significant differences in salivary pH and buffering capacity were found among the study groups (U Mann-Wthitney > 0.005). Conclusion: Patients with hypertension and treated with diuretics have a decreased salivary flow and an increased total protein concentration while ph and buffer capacity remained normal.

Acute toxicity and diuretic studies of the roots of Asparagus racemosus willd in rats / Toxicidad aguda y estudios diuréticos del espárrago racemoso willd en ratas

OBJECTIVE: Asparagusracemosus Willd has been used as diuretic in Ayurveda but has not been validated by a suitable experimental model. Hence the present study was undertaken. MATERIALS AND METHODS: The study was carried out with an aqueous extract of the roots of Asparagus racemosus utilizing three doses viz 800 mg/kg, 1600 mg/kg and 3200 mg/kg for its diuretic activity in comparison with standard drug (furosemide) and control (normal saline) rats after doing acute toxicity study. RESULTS: Acute toxicity study showed no fatality even with the highest dose and the diuretic study revealed significant diuretic activity (p < 0.05) in the dose of 3200 mg/kg. CONCLUSION: Asparagus racemosus showed diuretic activity at a 3200 mg/kg dose without acute toxicity.

OBJETIVO: El espárrago racemoso Willd ha sido usado como diurético en ayurveda pero no ha sido validado mediante un modelo experimental conveniente. De ahí la razón para emprender el presente estudio. MATERIALES Y MÉTODOS: El estudio fue realizado con extracto acuoso de raíces de espárrago racemoso, utilizando tres dosis, a saber, 800 mg/kg, 1600 mg/kg y 3200 mg/kg para analizar su actividad diurética, comparándolo con el medicamento estándar (furosemida), y ratas de control (solución salina normal) después de hacer un estudio de toxicidad aguda. RESULTADOS: El estudio de toxicidad aguda no mostró fatalidad, incluso con la dosis más alta, y el estudio del diurético reveló una actividad diurética significativa (p < 0.05) con la dosis de 3200 mg/kg. CONCLUSIÓN: El espárrago racemoso mostró actividad diurética en una dosis de 3200 mg/kg sin toxicidad aguda.

Diuretic effect of powdered Cerasus avium [cherry] tails on healthy volunteers

In this study, the diuretic activity of powdered cherry stalk was evaluated in 13 healthy volunteers by means of their water balance. In addition to biochemical parameters, such as urinary electrolyte concentration, osmolality and any adverse reaction were determined. The capsules of cherry stalks were administered at an equivalent dose of 2.0 grams of the plant per person. Urinary biochemical determination was made of concentration of electrolytes [sodium, potassium, chloride and calcium], urinary volume and osmolality by standard laboratory procedures. Statistical evaluation was performed by Student's-t and Wilcoxon rank tests. After administration of cherry stalk, the mean of urine calcium, sodium, chloride, and urine volume increased, but the amount of urine potassium and urine osmolality did not change. No adverse reaction was observed. Powdered C. avium stalk increased mild urine volume confirming thus the claimed diuretic effect of the herb. Administration of cherry stalk caused urinary sodium and chloride rising less than loop diuretics but higher than the others. Because of rising calcium excretion, it should be used with cautious in those with urolithiasis

Matching salt intake to physiological need in rats using foraging protocols

Several studies of the quantitative relationship between sodium need and sodium intake in rats are reviewed. Using acute diuretic treatment 24 h beforehand, intake matches need fairly accurately when intake is spread out in time by using a hypotonic solution of NaCl. In contrast, using a hypertonic solution, intake is typically double the need. Using the same diuretic treatment, although the natriuresis occurs within ~1 h, the appetite appears only slowly over 24 h. Increased plasma levels of aldosterone parallel the increased intake; however, treatment with metyrapone blocks the rise in aldosterone but has no effect on appetite. Satiation of sodium appetite was studied in rats using sodium loss induced by chronic diuretic treatment and daily salt consumption sessions. When a simulated foraging cost was imposed on NaCl access in the form of a progressive ratio lever press task, rats showed satiation for NaCl (break point) after consuming an amount close to their estimated deficit. The chronic diuretic regimen produced hypovolemia and large increases in plasma aldosterone concentration and renin activity. These parameters were reversed to or toward non-depleted control values at the time of behavioral satiation in the progressive ratio protocol. Satiation mechanisms for sodium appetite thus do appear to exist. However, they do not operate quantitatively when concentrated salt is available at no effort, but instead allow overconsumption. There are reasons to believe that such a bias toward overconsumption may have been beneficial over evolutionary time, but such biasing for salt and other commodities is maladaptive in a resource-rich environment.

Sodium transporters in kidney role in health and disease.

Sodium is an important cation and has an important role in BP regulation and ECF balance. Kidney plays an important role in sodium balance. Almost 99% of filtered sodium is reabsorbed. The absorption occurs via sodium transporters located in the various segments of the nephron. Each of these transporters has unique features and is blocked by a specific diuretic. The activating and inactivating mutations of these transporters are associated with important clinical syndromes. The understanding of these transporters and their mutations is essential for proper diagnosis and management of syndromes associated with the defects of these transporters. Also the knowledge of sodium transporters helps in understanding the role of kidney in pathogenesis of hypertension and pharmacodynamics of diuretic action.

Comparison of the diuretic effects of frusemide and the Karavi Panchaka Ayurveda decoction.

OBJECTIVE: To investigate the diuretic, natriuretic and kaliuretic effects of the antihypertensive Ayurveda drug Karavi Panchaka decoction and compare it with the diuretic frusemide. DESIGN: An animal study using Sprague-Dawley rats. The volume of urine and the total sodium and potassium excreted in the urine by rats in response to orally fed Karavi Panchaka decoction were compared with rats fed with frusemide. Control experiments were done with rats receiving similar volumes of distilled water orally. The Ayurveda drug was prepared in accordance with the traditional method in the laboratory using medicinal plant specimens individually collected and identified. MEASUREMENTS: The volume of urine excreted during a 24-hour period following administration of the Ayurveda drug, frusemide or water was measured.The total sodium and potassium ion concentrations in the urine samples were determined using flame photometry. RESULTS: The Karavi Panchaka decoction clearly showed a statistically significant increase in urine excretion when compared with the control group that received only distilled water. The potassium ion excretion was significantly increased in the Karavi Panchaka decoction treated group when compared to the control group. This increase was statistically similar to that caused by frusemide. Neither drug had a significant effect on sodium ion excretion at the dosages used. CONCLUSION: Our results show that the Karavi Panchaka decoction significantly increases urine and potassium ion excretion in rats, but has no effect on sodium ion excretion at the dosage used. The effect of the Ayurveda drug on urine output as well as the sodium and potassium ion excretion is similar to that of frusemide administered at the dose used in our study.

Bioactivity of marine organisms: Part IX--screening of some marine flora from the Indian coasts.

Alcoholic extracts of 48 identified species of marine flora were screened for a wide range of biological activities. Of these, 3 extracts showed diuretic activity while 2 extracts showed hypotensive effect.

Efeitos farmacológicos dos diuréticos e dos bloqueadores dos canais de cálcio / Pharmacological effects of diuretics and calcium channel blockers

Os diuréticos têm sido utilizados no tratamento de pacientes hipertensos durante as últimas quatro décadas. São tão eficazes quanto a maioria de outros agentes anti-hipertensivos. Administrados como monoterapia ou em associação com outros agentes, formam a base terapêutica para a maioria dos pacientes hipertensos. Os tiazídicos são usualmente os de primeira escolha, geralmente em associação com outras drogas anti-hipertensivas. Os diuréticos de alça são indicados para pacientes com insuficiência renal, hipertensão resistente ou falência cardíaca. Os diuréticos são prescritos para pacientes hipertensos principalmente por: (1) sua eficácia, baixo custo e poucos efeitos colaterais; (2) seu efeito sinérgico, quando em associação com outros agentes anti-hipertensivos; (3) impedir a retenção de sal e fluido causado por outros agentes anti-hipertensivos e (4) sua utilidade em pacientes com falência cardíaca. Os bloqueadores de canais de cálcio (BCC) constituem um grupo estrutural e funcionamento heterogêneo, e são freqüentemente usados no tratamento de pacientes com hipertensão e angina. Incluem as dihidropiridinas, como a nifedipina e o anlodipino e as não-dihidropiridinas como o verapamil e o diltiazem. Como classe são bem tolerados e exibem poucos efeitos colaterais. Apesar da preocupação com a segurança no seu uso, dados recentes de ensaios clínicos, em larga escala, não demonstraram associação dos BCC de longa duração e os eventos cardiovasculares. Mesmo assim o uso dos BCC foi associado a aumento do risco de falência cardíaca. A partir desses resultados, pode-se concluir que os BCC de longa duração podem ser usados no tratamento da hipertensão e angina. Entretanto, como classe não são tão protetores quanto os outros agentes anti-hipertensivos na falência cardíaca

Transcranial Doppler ultrasound analysis of resistive index in rostral and caudal cerebral arteries in dogs

Transcranial Doppler (TCD) was carried out to determine the resistive index (RI) values of normal canine cerebral arteries and its reproducibility and to evaluate the change of cerebral vascular resistance following diuretics administration. RI values of rostral cerebral artery (RCA) were compared between fontanelle window and temporal window. Normal ranges and reproducibility of the RI values were examined in the rostal cerebral artery (RCA) and caudal cerebral artery (CCA). And after administration of diuretics, TCD-derived RI values were measured at RCA and CCA. Cerebral vascular RI values of RCA and CCA were 0.55 +/- 0.05 and 0.55 +/- 0.03 in the normal dogs, respectively. There was no significant difference of RI between male and female; between fontanelle window and temporal window. Reproducibility of RI measurements between intraobserver and interobserver were relatively high. The RI of RCA and CCA were significantly increased 15 minutes after mannitol administration (p<0.01) and returned to baseline values by 30 minutes, but it did not significantly change after furosemide and saline administration. The results suggest that TCD is a useful test which can obtain reproducible results from any window and has the advantage of detecting subtle changes in cerebral vascular resistance.

hipertensão arterial / hypertension

A hipertensão (pressão sistólica >= 140 mmhg ou díastólíca >= 90 mmhg) tem alta prevalência em países desenvolvidos. Ocorre em um a cada quatro indivíduos em determinada comunidade e indivíduos normotensos'com mais de 50 anos tem 90por cento de chance de desenvolver um aumento da pressão arterial durante os próximos 25 anos. A prevalêncía é maior entre negros e idosos, especialmente mulheres idosas. O risco cardiovascular da hipertensão sistálica se inicia em 115 mmhg e o risco da hipertensão diastólica começa em 75 mmhg. O JNC 7 Report demonstrou que o peso/risco da hipertensão (ataque cardíaco, doença cardíaca, derrame, doença renal) pode ser atenuado com a diminuição da pressão arterial através de um novo nível objetivado de 120/80 mmhg. A medida exata da pressão arterial e a verificação da pressão elevada sobre múltiplas ocasiões há muito tempo são importantes. A pressão arterial que está elevada onde a duração medida em uma visita ao consultório, mas que é, por outro lado, normal (hipertensão do avental branco), pre- sente em 20 por cento dos pacientes com pressão arterial elevada, pode ser um precursor de hipertensão sancionada e, por essa razão, garantia de advertência. A avaliação poderia identificar sinais cardiovascular, cerebrovascular ou doença vascular periférica, bem como outros fatores de risco cardiovascular comumente presentes com hipertensão. Análise urinária, contagem completa de hemácías, 12-lead eletrocardíografia, testes químicos sanguíneos (creatinina, sódio, potássio, fasting glucose, colesteroi total e lipoproteína de alta densidade) são rotineiramente indicados. A maior parte dos casos de hipertensão pode ser prevenida e controlada, mas isso requer entrega de tarefas. O objetivo primário do tratamento é prevenir a doença cardiovascular e a morte. Intervenções no estilo de vida seriam defendídas como a primeira linha de tratamento em todos os casos.

Hipertensäo arterial / Hypertension

A hipertensäo arterial representa um dos mais significativo fator de risco para doença cardiovascular, principalmente quando vem acompanhado de diabetes, hipercolesterolemia, tabagismo e hipertrofia ventricular esquerda. A maioria dos hipertensos é do tipo essencial e a forte suspeita clínica deverá apontar para a investigaçäo ded uma causa secundária de etiologia endócrina, iatrogênica, de origem vascular ou renal vascular ou parenquimatosa. O tratamento näo farmacológico e mudança de hábito deveräo sempre estar recomendada. Observando-se principalmente reduçäo na ingestäo de sal, perda de peso, implementaçäo de exercícios. O tratamento farmacológico poderá ser iniciado com um diurético tiazídico, ou beta-bloqueador, ou antagonista de canal de cálcio, ou inibidor de ECA, ou um sartam ou mesmo combinaçäo de droga. Deve-se contemplar na decisäo de tratamento;1) o nível da pressäo arterial ( caso a pressäo arterial esteja maior ou igual 160/90mmHg se sugere iniciar com combinaçäo ded droga; 2) a presença de outros fatores de risco ou de complicaçöes cardioavsculares. O médico deverá perseguir o controle efetivo da pressäo arterial ( número ideal < 135/85 mmHg) e para isso é possivel a necessidade de se empregar mais de um agente anti-hioertensivo. Deve-se estar atento que a aderência ao tratamento é em geral, muito baixa, comprometendo o resultado final.(au)

Abordagem farmacológica da hipertensäo em diabéticos / Pharmacological approach of hypertension in diabetics

Objetivos: Determinar a prevalência de hipertensos com diabetes mellitus (DM) numa populaçäo de hipertensos atendidos no ambulatório ded Medicina Interna do Hospital Universitário (HU) da Universidade Federal de Santa Catarina, verificando as classes de anti-hipertensivos mais prescritas e se sua utilizaçäo encontra respaldo na literatura especializada. Métodos : Estudo observacional, descritivo e transversal, realizado no período de janeiro a junho de 1999, com uma populaçäo de 580 pacientes hipertensos, buscando entre esses, os portadores de DM. Foram analisados dados sobre idade,raça, tipo de DM e o(s)último(s) medicamento(s) prescrito(s) no ano de 1999. Resultados: Dos 580 hipertensos, 168 eram portadores de DM, estabelecendo-se uma prevalência ded 29(pro cento) de hipertensos diabéticos. A maioria tinha 60 anos ou mais (110/168 - 65,5 (por cento) , era do sexo feminino ( 131/168 - 78 (porcento)) ,brancos ( 146/168 - 86,9(por cento) e portadores de DM tipo 2 ( 164/168 - 97,6 ( por cento). Considerando as prescriçöes/droga, os diuréticos foram as drogas mais prescritas ( 105/240 - 44,7 ( por cento)), seguidos pelos inibidores da enzima conversora de angiotensina ( IECA) 71/240 - 29,6 (por cento)). Na monoterapia, predominaram os IECA ( 30/76 - 39,5( por cento)) e na terapia combinada prevaleceu a associaçäo de diuréticos e IECA ( 27/74 - 36,5 ( por cento)). Conclusöes : A prevalência de DM em hipertensos foi de 29(por cento). As drogas mais prescritas foram diuréticos e IECA, tanto em monoterapia quanto em associaçäo. O efeito benéfico, obtido através da combinaçäo dessas drogas, proporciona ao paciente hipertenso diabético bom controle pressórico, diminuiçäo da morbimortalidade cardiovascular e proteçäo aos órgäos-alvo(au)