The mechanism of blood pressure regulation by high potassium diet in the kidney / 生理学报

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.

Anatomy and micromorphometric analysis of leaf Catasetum x apolloi Benelli & Grade with addition of potassium silicate under different light sources / Anatomia e análise micromorfométrica foliar de Catasetum x apolloi Benelli & Grade com adição de silicato de potássio em diferentes fontes de luz

Abstract The aim of this study was to compare vitroplants Catasetum x apolloi grown under natural light and artificial light and different concentrations of potassium silicate, providing data on the anatomical differentiation that aids the acclimatization process of this species. Plants from in vitro seeding were used; 5 protocorms of approximately 0.5 cm were inoculated into vials with a capacity of 500 mL containing 100 mL of alternative culture medium plus potassium silicate (0.0, 0.5; 1.0 mL L–1), pH adjusted to 5.5 ± 0.5 and gelated with 4GL–1 agar before the autoclaving process. Cultures were maintained under natural light (TNE) and artificial light (TAE) for 90 days, and micromorphometric analysis was performed for polar and equatorial diameter, density and stomatal index, blade thickness in the central rib, and secondary veins. Applications in K2SiO4 alternative medium provided the following: elongation of the hypodermis, thicker mesophyll, and more prominent midrib; elipptical guard cells; formation of epistomatal chamber; and lower stomatal density and stomatal with lower equatorial and polar diameters. The conditions that favored the acclimatization were lower light intensities and lower potassium silicate doses.

Resumo O objetivo desse trabalho foi comparar vitroplantas de Catasetum x apolloi cultivadas sob luz natural e luz artificial e diferentes concentrações de silicato de potássio, fornecendo dados sobre diferenciação anatômica que auxiliem no processo de aclimatação dessa espécie. Utilizou-se plantas provenientes da semeadura in vitro, 5 protocormos de aproximadamente 0,5 cm foram inoculados em frascos com capacidade para 500 mL contendo 100 mL de meio de cultura alternativo, acrescido de silicato de potássio (0,0; 0,5; 1,0 mL L–1), pH ajustado para 5,5 ±0,5 e gelificado com 4gL–1 de ágar antes do processo de autoclavagem. As culturas foram mantidas sob luz natural (TAA) e luz artificial (TAN) por 90 dias, e feitas análises micromorfométricas (diâmetro polar e equatorial, densidade e índice estomático, espessura do limbo na nervura central e nervuras secundárias). As aplicações de K2SiO4 em meio alternativo, propiciaram: alongamento da hipoderme; mesofilo mais espesso e nervura central mais proeminente; células guardas elípticas; formação de câmaras supraestomáticas; menor densidade estomática e estômatos com menores diâmetros equatorial e polar. As condições que podem favorecer a aclimatação são menores intensidades de luz e menores doses de silicato de potássio.

Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.

Development of cardioplegic solution without potassium: experimental study in rat / Desenvolvimento de solução cardioplégica sem potássio: estudo experimental em ratos

INTRODUCTION: Myocardial preservation during open heart surgeries and harvesting for transplant are of great importance. The heart at the end of procedure has to resume its functions as soon as possible. All cardioplegic solutions are based on potassium for induction of cardioplegic arrest. OBJECTIVE: To assess a cardioplegic solution with no potassium addition to the formula with two other commercially available cardioplegic solutions. The comparative assessment was based on cytotoxicity, adenosine triphosphate myocardial preservation, and caspase 3 activity. The tested solution (LIRM) uses low doses of sodium channel blocker (lidocaine), potassium channel opener (cromakalin), and actin/myosin cross bridge inhibitor (2,3-butanedione monoxime). METHODS: Wistar rats underwent thoracotomy under mechanical ventilation and three different solutions were used for "in situ" perfusion for cardioplegic arrest induction: Custodiol (HTK), Braile (G/A), and LIRM solutions. After cardiac arrest, the hearts were excised and kept in cold storage for 4 hours. After this period, the hearts were assessed with optical light microscopy, myocardial ATP content and caspase 3 activity. All three solutions were evaluated for direct cytotoxicity with L929 and WEHI-164 cells. RESULTS: The ATP content was higher in the Custodiol group compared to two other solutions (P<0.05). The caspase activity was lower in the HTK group compared to LIRM and G/A solutions (P<0.01). The LIRM solution showed lower caspase activity compared to Braile solution (P<0.01). All solutions showed no cytotoxicity effect after 24 hours of cells exposure to cardioplegic solutions. CONCLUSION: Cardioplegia solutions without potassium are promised and aminoacid addition might be an interesting strategy. More evaluation is necessary for an optimal cardioplegic solution development.

INTRODUÇÃO: Preservação do miocárdio durante cirurgias cardíacas abertas e de colheita para transplante são de grande importância. O coração ao final do processo tem de retomar as suas funções, logo que possível. Todas as soluções cardioplégicas são baseadas em potássio, para indução de parada cardioplégica. OBJETIVO: Comparar a uma solução cardioplégica sem adição de potássio à sua fórmula com duas outras soluções cardioplégicas disponíveis comercialmente. A avaliação comparativa foi baseada na citotoxicidade, preservação miocárdica (adenosina trifosfato, ATP) e atividade da caspase 3. A solução testada (LIRM) utiliza baixas doses de bloqueador de canal de sódio (lidocaína), abridor do canal de potássio (cromacalina) e inibidor da ponte actina/miosina (2,3-butanodiona monoxima). MÉTODOS: Ratos Wistar foram submetidos à toracotomia sob ventilação mecânica e três soluções diferentes foram utilizadas para perfusão in situ para a indução de parada cardioplégica: soluções Custodiol (HTK) Braile (G/A) e LIRM. Após parada cardíaca, os corações foram retirados e mantidos em câmara fria por 4 horas. Após esse período, o coração foi avaliado com microscopia de luz ótica, o conteúdo de ATP miocárdico e atividade da caspase 3. Todas as três soluções foram avaliadas quanto à citotoxicidade direta com células L929 e WEHI-164. RESULTADOS: A quantidade de ATP foi maior no grupo Custodiol em comparação às com outras duas soluções (P<0,05). A atividade de caspase foi menor no grupo HTK quando comparado às soluções LIRM e G/A (P<0,01). A solução LIRM demonstrou menor atividade da caspase em comparação à solução Braile (P<0,01). Todas as soluções não mostraram qualquer efeito de citotoxicidade após 24 horas de exposição das células às soluções cardioplégicas. CONCLUSÃO: Soluções cardioplégicas sem potássio são uma perspectiva e a adição de aminoácido pode ser uma estratégia interessante. Mais avaliações são necessárias para o desenvolvimento ideal da solução cardioplégica.

The effect of nitrogen and potassium fertilizers on growth parameters and carbohydrate contents of sweet sorghum cultivars.

Sweet sorghum is tolerant to high temperature and drought and can be considered as an alternative crop to sugar beet and maize in Iran. In this study, the effects of nitrogen and potassium fertilizers on growth parameters including stem height, stem diameter, stem fresh weight, total fresh weight; carbohydrate contents including total sugar, brix value, sucrose content and purify; and juice extract of two sweet sorghum cultivars were determined. Three rates of N-fertilizer (0, 90, 180 kg urea ha(-1)) and two rates of K fertilizer (0 and 50 kg potassium sulfate ha(-1)) assigned as main plots and two sweet sorghum cultivars (Rio and Keller) as subplots. Growth parameters at soft dough and physiological maturity stages and carbohydrate contents at physiological maturity stage were determined. Results showed that application of 180 kg urea ha(-1) as compared to control at physiological maturity significantly (p < 0.01) increased stem height (12.65%), stem fresh weight (24.57%), total fresh weight (78.22%), total sugar (39.25%), sucrose content (9%) and juice extract (34.96%). Application of 50 kg potassium sulfate ha(-1) increased (p < 0.05) stem fresh weight (24.33%), total fresh weight (25.44%), total sugar (10.50%), and juice extract (9%) at physiological maturity. The highest growth parameters, carbohydrate contents and juice extract were obtained with the application of 180 kg urea ha(-1) and 50 kg potassium sulfate ha(-1) using cultivar (cv) Keller. The best results were taken with the application of both fertilizers.

Changes in Inward Rectifier K+ Channels in Hepatic Stellate Cells During Primary Culture

PURPOSE: This study examined the expression and function of inward rectifier K+ channels in cultured rat hepatic stellate cells (HSC). MATERIALS AND METHODS: The expression of inward rectifier K+ channels was measured using real-time RT-PCR, and electrophysiological properties were determined using the gramicidin-perforated patch-clamp technique. RESULTS: The dominant inward rectifier K+ channel subtypes were K(ir)2.1 and K(ir)6.1. These dominant K+ channel subtypes decreased significantly during the primary culture throughout activation process. HSC can be classified into two subgroups: one with an inward-rectifying K+ current (type 1) and the other without (type 2). The inward current was blocked by Ba2+ (100micrometer) and enhanced by high K+ (140mM), more prominently in type 1 HSC. There was a correlation between the amplitude of the Ba2+-sensitive current and the membrane potential. In addition, Ba2+ (300micrometer) depolarized the membrane potential. After the culture period, the amplitude of the inward current decreased and the membrane potential became depolarized. CONCLUSION: HSC express inward rectifier K+ channels, which physiologically regulate membrane potential and decrease during the activation process. These results will potentially help determine properties of the inward rectifier K+ channels in HSC as well as their roles in the activation process.

Effects of Polyamines on Contractility of Guinea-Pig Gastric Smooth Muscle

This study was designed to investigate the effects of polyamines on mechanical contraction and voltage-dependent calcium current (VDCC) of guinea-pig gastric smooth muscle. Mechanical contraction and calcium channel current (I(Ba)) were recorded by isometric tension recording and whole-cell patch clamp technique. Spermine, spermidine and putrescine inhibited spontaneous contraction of the gastric smooth muscle in a concentration-dependent manner. Spermine (2 mM) reduced high K+ (50 mM)-induced contraction to 16+/-6.4% of the control (n=9), and significantly inhibited I(Ba) in a reversible manner (p<0.05; IC50=0.8 mM). Pre- and post-treatment of tissue with spermine (2-5 mM, n=10) also inhibited acetylcholine (10 micrometer)-induced phasic contraction to 5+/-6.4% of the control. Inhibitory effect of spermine on I(Ba) was observed at a wide range of test potentials of current/voltage (I/V) relationship (p<0.05), and steady-state activation of I(Ba) was shifted to the right by spermine (p<0.05). Spermidine and putrescine (1 mM each) also inhibited I(Ba) to 51+/-5.7% and 81+/-5.3% of the control, respectively. And putrescine (1 mM) inhibited I(Ba) at whole tested potentials (p<0.05) without significant change of kinetics (p<0.05). Finally, 5 mM putrescine also inhibited high K+ -induced contraction to 53+/-7.1% of the control (n=4). These findings suggest that polyamines inhibit contractions of guinea-pig gastric smooth muscle via inhibition of VDCC.

CFTR, a rectifying, non-rectifying anion channel?

No abstract available.

Solución GIK en el infarto agudo al miocardio: el resurgimiento de una antigua terapia / Glucose-insulin-K solution for acute myocardial infarction: rebirth of an old form of therapy

La terapia con solución de glucosa insulina y potasio en el infarto o solución GIK fue inicialmente utilizada por Sodi-Pallares. Desde entonces muchos trabajos con esta solución han sido publicados con resultados disímiles. Sin embargo el resultado de un meta-análisis reciente, que incluye sólo trabajos randomizados con dosis adecuadas de GIK, parece confirmar la disminución de la mortalidad asociada a solución GIK. Para comprender mejor los fundamentos y posibles mecanismos de beneficio con el empleo de la solución GIK en el infarto del miocardio, revisaremos primero el metabolismo miocárdico normal y en condiciones de isquemia, luego el daño por reperfusión post infarto y los efectos de la solución GIK en el miocardio. Por último, analizaremos las experiencias clínicas publicadas con esta terapia

Development of the insulin secretion mechanism in fetal and neonatal rat pancreatic B-cells: response to glucose, K+, theophylline, and carbamylcholine

We studied the development of the insulin secretion mechanism in the pancreas of fetal (19- and 21-day-old), neonatal (3-day-old), and adult (90-day-old) rats in response to stimulation with 8.3 or 16.7 mM glucose, 30 mM K + , 5 mM theophylline (Theo) and 200 µM carbamylcholine (Cch). No effect of glucose or high K + was observed on the pancreas from 19-day-old fetuses, whereas Theo and Cch significantly increased insulin secretion at this age (82 and 127 por cento above basal levels, respectively). High K + also failed to alter the insulin secretion in the pancreas from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose significantly stimulated insulin release by 41 and 54 percent above basal levels, respectively. Similar results were obtained with Theo and Cch. A more marked effect of glucose on insulin secretion was observed in the pancreas of 3-day-old rats, reaching 84 and 179 percent above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Theo and Cch increased insulin secretion to close to two-times basal levels. In islets from adult rats, 8.3 mM and 16.7 mM glucose, Theo, and Cch increased the insulin release by 104, 193, 318 and 396 percent above basal levels, respectively. These data indicate that pancreatic B-cells from 19-day-old fetuses were already sensitive to stimuli that use either cAMP or IP 3 and DAG as second messengers, but insensitive to stimuli such as glucose and high K + that induce membrane depolarization. The greater effect of glucose on insulin secretion during the neonatal period indicates that this period is crucial for the maturation of the glucose-sensing mechanism in B-cells

Comportamento motor, sob estímulo farmacológico, de segmentos duodenais pré e pós-papilar de ratos albinos / Motor reaction, under the pharmacological stimulus of the isolated duodenal pre-papillary and post papilary section of albino rats

Cada segmento do tubo digestivo tem um padrao próprio de motilidade e toda atividade motora resulta fundamentalmente das propriedades elétricas do músculo liso. Em sua atividade motora o duodeno apresenta funçoes de mistura e progressao, como também participa do controle do esvaziamento gástrico. Os movimentos do complexo antro-piloro-bulbar sao considerados ponto de partida para o peristaltismo intestinal, inclusive com movimentos reversos, sendo que encontramos normalmente uma diminuiçao progressiva da freqüência das ondas do duodeno ao íleo terminal. Considerando que o duodeno tem características embriológicas, anatômicas, histológicas e bioquímicas que o destacam na fisiologia digestiva, interessou-nos o comportamento motor do segmento duodenal pré e pós-papilar sob estímulo farmacológico. Na realizaçao do tranbalho foram utilizados dez ratos albinos dos quais foram retirados os segmentos duodenais pré e pós-papilar. Estes foram divididos em: grupos I e II, pré e pós-papilar, respectivamente. Em cada segmento foram obtidos as diferenças porcentuais (delta percentual) do número de ondas e da amplitude máxima no movimento espontaneo e sob estimulo farmacológico do cálcio, potássio, acetilcolina e nor-adrenalina. Foram analisados segundo a açao das drogas dentro de cada grupo e, também, analisadas a açao de cada droga, comparadas entre os grupos. Os resultados mostraram diferenças no D percentual do número de ondas sob estímulo farmacológico quando comparados ao movimento espontâneo. Na amplitude máxima, porém, nao houve diferença significante. Nas condiçoes de realizaçao do trabalho, pode-se concluir entao, que o comportamento motor sob estímulo farmacológico do segmento duodenal pré-papilar isolado de rato é diferente do pós-papilar.

In vitro antimicrobial activity of potash alum.

This study reports the bactericidal activity of potash alum when added to water, against various epidemic causing enteric pathogens like Vibrio cholerae 01, V. cholerae 0139 and Shigella dysenteriae 1 by lowering the pH of water (from 6.0 to 4.0). Growth of the enteric pathogens was monitored in vitro by inoculating broth cultures of the different organisms in distilled water containing increasing concentrations of potash alum and quantitatively determining the concentration of viable organisms over a 48 h period by the standard plate count method. Controls constituted cultures of each organism grown in the absence of potash alum. The pH of alum administered water was measured in each test tube before inoculation of organisms. Potash alum was found to inhibit growth (10(5) viable count per ml) of most of the organisms examined, particularly V. cholerae 01 and V. cholerae 0139 in a dose dependent fashion. Reduction of colony forming units was observed in presence of 0.25 g/dl of alum after 5 h and no growth was noticed after 24 h.

Causticum / Causticum

La presente publicación trata sobre el uso de Causticum en veterinaria homeopática. Este remedio es raramente prescripto como medicamento constitucional y frecuentemente es olvidado como remedio local en enfermedades respiratorias, articulares, neurológicas y de piel. Este trabajo tiene por objeto demostrar la acción de Causticum en desórdenes neurológicos, centrales y periféricos. Finalmente, se presentan cierto número de casos

Mecanismos involucrados en el efecto antiarritmico y proarritmico del magnesio / Mechanisms involved in the antiarrhythmic and proarrhythmic effects of magnesium

El objetivo fue analizar en perros, los efectos del MgCl2, y del MgSO4 sobre los mecanismos electrofisiológicos que pudieran vincularse con las acciones antiarrítmicas y proarrítmicas de estas soluciones. Se estudiaron previamente los parámetros farmacocinéticos del MgCl2 y del MgSO4; ambos mostraron que el Mg plasmático disminuye exponencialmente (constante beta de O,118 ñ O,013 h-l), t 1/2 de eliminación de 6,02 ñ O,68 h y una Vda de O,259 ñ O,02lxkg-l. Posteriormente se estudiaron dos grupos de animales - Grupo I: dieta normal. Grupo II A: dieta sin Mg + clortalidona + K y Grupo II B: dieta sin Mg + clortalidona + KCI + MgSO4. Se midieron los electrolitos y las variables electrofisiológicas por medio de estimulación ventricular programada. El grupo I mostró que la administración de MgSO4 endovenoso disminuye el Na, el K y el umbral de fibrilación ventricular (UFV) y prolonga el período refractaria efectivo ventricular (PREV). El MgCl2 no modifica el UFV, pero prolonga el PREV, el A-H, el QTc y el PQ. El MgSO4 aumenta la excreción de K urinario en forma significativamente mayor que el MgCl2. La administración de NaCl no alteró las variables electrofisiológicas pero el NaSO4 disminuyó el K plasmático, sin modificar el UFV. El Grupo II A presentó descenso del K y Mg plasmático, linfocitario y miocárdico, disminución del PREV y del UFV y aumento del QTc. A este grupo se le administro en forma aguda: 1) MgSO4 que provocó mayor descenso del UFV y del K plasmático y aumento del PREV y 2) KCI que aumento el K piasmático y el UFV. El grupo II B no modificó los electrolitos ni las variables electrofisiológicas. Se concluye que los efectos antiarrítmicos observados en clínica por la administración de sales de Mg se deberían probablemente a la prolongación del PREV. Sin embargo, la depleción de K inducida por el MgSO4 puede provocar un descenso del UFV, efecto proarrítmico que se podría evitar utilizando MgCl2.

Descriçäo compartimentalizada das dinâmicas iônicas intra e extracelulares de tecidos neuronais / Compartment description of intracellular and extracellular ionic dynamics of neuronal tissues

Em geral, a modelagem realística de sistemas neuronais considera os circuitos elétricos análogos aos mecanismos de geração de correntes elétricas, potenciais e campos elétricos, não considerando os de difusão e eletrodifusão. Entretanto, na simulação de fenômenos que envolvem grandes fluxos iônicos, tais como o fenômeno da Depressão Alastrante de Leão, onde esses mecanismos são comprovadamente essenciais, faz-se necessária a descrição das dinâmicas iônicas envolvidas. Com esse objetivo, este trabalho apresenta o desenvolvimento de uma representação compartimentalizada para as dinâmicas intra e extracelulares em tecidos neuronais, a qual pode ser verificada como representativa de um modelo analítico, de onde leis básicas, tais como a lei de Fick e a equação de Nerst, podem ser deduzidas.

Cardioprotective drugs decrease the Na+ background current

Cardiac dysfunctions such as myocardial functional failure and ventricular arrhythmia have been largely attributed to intracellular Ca2+ overload. One of the mechanisms of intracellular Ca2+ overload involves a rapid influx of Ca2+ via Na(+)-Ca2+ exchange during the reperfusion which utilizes the accumulation of Na+ in myocytes during ischemic cardiac arrest. Possible sources of the intracellular Na+ accumulation include Na+ channel, Na(+)-H+ exchange, Na(+)-Ca2+ exchange, and Na+ background current. In this study, we studied the role of the Na+ background current in intracellular Na+ accumulation during the cardiac arrest by measuring the Na+ background current in guinea pig ventricular myocytes with whole cell clamp method and evaluating the effects of cardioprotective drugs on the Na+ background current. The results were as follows: (1) The Na+ background inward current at -40 mV membrane potential was larger at Ca2+ free solution than 1.8 mM Ca2+ solution. (2) The Na+ background current was not affected by verapamil. (3) 2 microM O-(N, N-hexamethylene)-amiloride (HMA) decreased the Na+ background current at negative membrane potential. (4) The new cardioprotective drug, R 56865, decreased the Na+ background current. These results suggest that the Na+ background current plays a role in increasing the intracellular Na+ activity during high K+ cardioplegia and the blocking effect of myoprotective drugs, such as R 56865, on the Na+ background current may contribute to myocardial protection after cardioplegia.

Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells

We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms.

Effect of nifedipine and dipyridamole on K+ and NA stimulated 45Ca-uptake into rabbit aortic strips.

The effect of dipyridamole (DPM), a purine nucleoside uptake inhibitor, on the K+ and noradrenaline (NA)-stimulated 45Ca-uptake into Rabbit aortic strips was studied and compared with that of nifedipine (NFD). DPM (10(-6) M) significantly (P < 0.02) inhibited 45Ca-uptake in aortic strips stimulated with K+ (10(-1) M). However, it had less significant effect on NA (10(-4) M)-stimulated 45Ca-uptake. The percentage inhibition was 80 and 57 in K+ and NA-stimulated 45Ca-uptake, respectively. Similarly, NFD (10(-7) M) caused significant (P < 0.01, P < 0.05) decrease in K+ (0.060 +/- 0.009) and NA (0.082 + 0.01, mM)-stimulated 45Ca-uptake. The percentage inhibition by NFD was 98 and 64 in K+ and NA-stimulated 45Ca-uptake, respectively. The results suggest that DPM inhibits Ca2+ influx occurring through Voltage Operated Calcium Channels (VOCCs) but it has little effect on Receptor Operated Calcium Channels (ROCCs).

Análise dos efeitos colaterais provocados pelo uso da acetazolamida via oral nos primeiros 5 dias de tratamento com relaçäo aos níveis séricos de potássio / Side effects of acetazolamide per os during the first five days of treatment and relationship with seric potassium level

Os autores realizaram um estudo duplo-cego para determinar uma possível entre potássio sérico e efeitos colaterais, que aparecem nos primeiros 5 dias de tratamento com acetazolamida 500 mg, via oral. Em todos aqueles que usaram a droga produziu-se efeitos colaterais, sendo o mais comum parestesias. Näo houve diferença significativa entre os níveis de postássio sérico antes e após o tratamento

Effects of vanadate on vascular contractility and membrane potential in the rabbit aorta

Isolated rabbit aortic ring with intact endothelial cell preparations precontracted with NE (10(-7) M) were relaxed by vanadate in a dose dependent manner (from 0.2 to 2 mM). Application of vanadate and ACh during the tonic phase of high K+(100 mM)-induced contraction showed a slight relaxation in contrast to that in NE-induced contraction, but sodium nitroprusside (10 microM) more effectively relaxed the aortic ring preparations in high K+ contraction than that of vanadate. Vanadate-induced relaxation in NE-contracted aortic rings was reversed by application of BaCl2 (50 microM) or glibenclamide (10 microM). Furthermore, Vanadate hyperpolarized membrane potential of smooth muscle cells in endothelium-intact aortic strips and this effect was abolished by application of glibenclamide. The above results suggest that vanadate release EDHF (Endothelium-Derived Hyperpolarizing Factor), in addition to EDRF (Endothelium-Derived Relaxing Factor) from endothelial cell. This EDHF hyperpolarize the smooth muscle cell membrane potential via opening of the ATP-sensitive K+ channel and close a voltage dependent Ca++ channel. So it is suggested that the vanadate-induced relaxation of rabbit thoracic aortic rings may be due to the combined effects of EDRF and EDHF.