Curva de crescimento em altura na cernelha de equinos da raça Mangalarga Marchador considerando-se heterocedasticidade / Growth curve for height at withers of Mangalarga Marchador horses with heterocedasticity

Objetivou-se, com este estudo, avaliar o ajuste dos modelos de Brody, Gompertz, Logístico e Von Bertalanffy aos dados de altura na cernelha de equinos Mangalarga Marchador, ponderando pelo inverso da variância, a fim de selecionar o melhor modelo e predizer sobre o crescimento e a maturidade dos animais dessa raça. Foram utilizados dados de 230 equinos dos seis aos 176 meses de idade, os quais foram divididos por sexo e em 16 classes de idade. Os modelos estudados foram comparados segundo os avaliadores de qualidade: coeficiente de determinação (R2); desvio padrão residual (DPR) e critério de informação de Akaike (AIC). A estimação dos parâmetros dos modelos foi realizada pelo método de mínimos quadrados ponderado no software R. Todos os modelos avaliados se mostraram adequados para descrever a curva de crescimento em ambos os sexos. Perante os avaliadores utilizados, o modelo Logístico foi o mais adequado para descrever as curvas de crescimento em altura na cernelha nos dois sexos da raça Mangalarga Marchador. Observou-se também um crescimento acelerado nos primeiros meses de idade. Os animais machos atingiram uma altura adulta maior, porém as fêmeas são mais precoces, pois apresentaram maior estimativa para o índice de maturidade.(AU)

This work aimed to evaluate the fit of models Brody, Gompertz, Logistic and Von Bertalanffy to height at the withers of Mangalarga Marchador horses, weighed by the inverse of variance, in order to select the best model and predict growth and maturity of this breed pf animals. We used data of 230 equines from 06 to 176 months of age who were divided by sex and 16 age classes. The models were compared according to the quality assessors: coefficient of determination (R2); residual standard deviation (RSD) and Akaike information criteria (AIC). The estimation of the parameters from models was performed by the weighted least squares method in Software R. All models evaluated were suitable to describe the growth curve in both sexes. In view of the evaluators used, the logistic model was the most suitable to describe the growth curves in withers height in both sexes for the race Mangalarga Marchador. A strong growth at first age was also observed. The males reached a greater adult height, but females did so sooner, because they presented higher estimates for the maturity index.(AU)

Validação do Nanolipe ® como método para determinar a digestibilidade aparente dos nutrientes pelos equinos / Validation of Nanolipe ® as method to assess the apparent digestibility of nutrients on horses

O NANOLIPE® é o indicador de digestibilidade LIPE® com incorporação de nano partículas que se misturam de forma mais homogênea e rápida na digesta, permitindo redução do período de adaptação e maiores taxas de recuperação daquele quando comparado com outros indicadores usados em equinos. Objetivou-se neste trabalho comparar a digestibilidade dos nutrientes de dieta em equinos obtida pelo método padrão (coleta total de fezes - CTF), estimada por dois indicadores internos (fibra em detergente ácido indigestível - FDAi; lignina Klason - LK) e por indicador externo NANOLIPE®, visando à validação deste último para uso na nutrição equina. Em delineamento de blocos ao acaso, oito éguas Mangalarga Marchador adultas (média de 380kg PV) foram usadas para avaliação dos tratamentos (CTF, FDAi, LK, NANOLIPE®). A dieta foi composta por 1,5% PV de feno de coast cross, 1,0% PV de concentrado comercial com 13% PB, dividido em dois tratos diários fornecidos às oito e às 17h, além de água e sal mineral à vontade. O experimento teve duração de 13 dias, sendo os oito iniciais para adaptação à dieta e ao manejo e os cinco finais para coleta de fezes. O NANOLIPE® foi fornecido no terceiro e quarto dias da coleta de fezes, sendo administrado uma vez por dia, por meio de cápsulas de 0,25g/animal/dia via oral. Houve diferença (P<0,05) entre os valores de produção fecal estimados pela FDAi (0,86kg MS) e LK (0,60kg MS) em comparação aos observados na CTF (2,16kg MS) e NANOLIPE® (2,17kg MS), com sub ou superestimação dos coeficientes de digestibilidade da MS, FDN, FDA, HEM, ED, MO e PB estimados pelos indicadores internos. O NANOLIPE® obteve alta taxa de recuperação (100,46%) e os coeficientes de digestibilidade de todos nutrientes foram semelhantes aos obtidos pela CTF. O indicador NANOLIPE® foi eficiente para estimativa da produção fecal e digestibilidade aparente dos nutrientes da dieta em equinos, quando fornecido por dois dias, sendo uma aplicação diária e com início da coleta de fezes, 24 horas após sua administração.(AU)

NANOLIPE® is the LIPE®digestibility indicator incorporating nano particles that blend more smoothly and quickly in digesta, allowing reduction of the induction period, and higher recovery rates that compared with other indicators used in horses. The objective of this work was to compare the digestibility of the diet of nutrients in horses obtained by standard method (total collection of feces - TCF) and estimated by two internal indicators ( Klason Lignin - KL and indigestible Acid Detergent Fiber.- iADF) ) and external indicator NANOLIPE®, aiming to validate the latter for use in equine nutrition. In a randomized block design, eight Mangalarga Marchador adult mares were used to evaluate treatments (CBC, iADF, LK, NANOLIPE®). The diet was composed of 1.5% PV hay Coast Cross, 1.0% PV of commercial concentrate, divided into two daily treatment.. The trial lasted 13 days, with 8 adaptation to the diet and the handling and 5 for the experimental procedures. In the first five days of the experimental period total feces was collected and in the 3th and 4th day the animals received NANOLIPE® administered once a day through capsules of 0.25 g / animal / day orally. Using the method of TFC as standart, the Klason Lignin and iADF proved inadequate (P<0,05) and NANOLIPE® was considered efficient (P>0,05) for estimating the digestibility of nutrients in the equine species. There were differences (P <0.05) between fecal production values estimated by iADF (0.86 kg DM) and LK (0.60 kg DM) compared to those observed in CTF (2.16 kg DM) and NANOLIPE® (2.17 kg DM) with under- or overestimation of the digestibility of DM, NDF, ADF, HEM, ED, OM and CP estimated by internal indicators. The NANOLIPE® got high recovery rate (100.46%) and the digestibility coefficients of all nutrients were similar to those obtained by the CTF. The NANOLIPE® indicator was efficient to estimate fecal output and apparent digestibility of dietary nutrients in horses when provided for two days, with a daily application and start collecting feces 24 hours after administration.(AU)

Feeding frequency and growth performance of juvenile pink shrimp ([farfantepenaeus paulensis) / Frequência de oferta alimentar e desempenho zootécnico de juvenis do camarão rosa (farfantepenaeus paulensis)

It is generally believed that increasing feeding frequency has immediate benefits, including reduced nutrient leaching and increased shrimp growth. In this context, the aim this work was to evaluate the effect of feeding frequency in growth performance of Farfantepenaeus paulensis. Juveniles of Farfantepenaeus paulensis were grown for 30 days in pen enclosures, at a stocking density of 5 shrimp/m2. The shrimp were fed on feeding trays at a rate of 8% of their biomass per day, with treatments of one, two, three and four times per day, with four replicates each. The results showed no differences (5% probability) in biomass gain of F. paulensis when feed was offered two, three or four times per day. However, it was observed that the once a day frequency had a negative influence on weight gain for this species of shrimp. We conclude that the supply of food with 35% crude protein twice a day is sufficient for the growth of F paulensis. Feeding frequency of three or four times can provide increased spending in the cultivation of juveniles of this species.

Acredita-se que uma frequência maior de alimentação traz benefícios imediatos, incluindo a redução da lixiviação de nutrientes e o aumento do crescimento do camarão. Nesse contexto, o objetivo do presente trabalho foi avaliar o efeito de diferentes frequências de oferta de alimento sobre o crescimento de Farfantepenaeus paulensis. Juvenis de Farfantepenaeus paulensis foram criados por 30 dias em tanques-rede, na densidade de estocagem de cinco camarões/m 2. Os camarões foram alimentados em comedouros com 8% da sua biomassa/dia, ofertados em parcelamentos de uma, duas, três e quatro vezes ao dia, com quatro repetições para cada tratamento. Os resultados mostraram que não ocorreram diferenças (5% de probabilidade) no ganho de biomassa de F. paulensis quando a frequência alimentar foi de duas, três ou quatro vezes ao dia. No entanto, os dados indicam que a frequência alimentar de uma vez ao dia interferiu negativamente no ganho de peso dessa espécie. Conclui-se que o fornecimento de ração com 35% de proteína bruta duas vezes ao dia é suficiente para o crescimento de F paulensis. O fornecimento de alimento três ou quatro vezes ao dia poderia acarretar maiores gastos no manejo de juvenis dessa espécie.

Integrated multi-trophic culture of Nile tilapia (Oreochromis niloticus) and Amazon river prawn (Macrobrachium amazonicum) in brackish water / Cultivo multi-trófico integrado de tilápia-do-nilo (Oreochromis niloticus) e camarão da Amazônia (Macrobrachium amazonicum) em água salobra

The aim of this study was to assess the feasibility of integrated multi-trophic culture of Nile tilapia (Oreochromis niloticus) and Amazon River prawn (Macrobrachium amazonicum) in brackish water by evaluating its limnological characteristics and economic performance. The experiment was completely randomized with four treatments and four repetitions: control treatment with Nile tilapia only, stocked with 2 tilapias/m² (P2C0) and three integrated multi-trophic culture treatments stocked with 2 tilapias/m² and prawns at densities of 4, 8 and 16 prawns/m² (P2C04, P2C08 and P2C16, respectively). The limnological variables of temperature, pH, dissolved oxygen, turbidity, ammonia, orthophosphate and chlorophyll "a" were evaluated and throughout the experiment remained within the limits recommended for culture. The experiment lasted 150 days with monthly animal sampling. No significant differences were observed for total fish biomass or for fish and prawn total survival rates. However, prawn individual weight decreased as stocking density increased. Gross revenue was not significantly different between treatments, as well as profitability. The profitability was 40.1% (P2C0), 36.7% (P2C04), 41.2% (P2C08) and 50.1% (P2C16). It is concluded that although feasible from the view point of husbandry, the integrated multi-tropic culture of M. amazonicum and O. niloticus did not influence significantly profitability compared to the monoculture system.

O objetivo deste estudo foi verificar a viabilidade do cultivo multitrófico integrado da tilápia-do-nilo (Oreochromis niloticus) e do camarão-da-amazônia (Macrobrachium amazonicum) em água salobra, mediante a avaliação de suas características limnológicas e de seu desempenho econômico. O experimento foi inteiramente ao acaso, com quatro tratamentos e quatro repetições: tratamento controle somente com tilápia-do-nilo, estocado com duas tilápias/m² (P2C0) e três tratamentos de cultivo multitrófico integrado, estocados com duas tilapias/m² e camarões nas densidades de quatro, oito e 16 camarões/m² (P2C04, P2C08 e P2C16, respectivamente). As variáveis limnológicas temperatura, pH, oxigênio dissolvido, turbidez, amônia, ortofosfato e clorofila "a" foram avaliadas e, durante todo o experimento, mantiveram-se dentro dos limites recomendados para o cultivo. O experimento durou 150 dias, com amostragem mensal dos animais. Diferenças significativas não foram observadas para a biomassa total de peixe nem para a taxa de sobrevivência total em peixes e camarões. Entretanto, o peso individual do camarão diminuiu à medida que a densidade de estocagem aumentou. A receita bruta não foi significativamente diferente entre os tratamentos, assim como a rentabilidade. A rentabilidade foi 40,1% (P2C0), 36,7% (P2C04), 41,2% (P2C08) e 50,1% (P2C16). Conclui-se que, apesar de viável do ponto de vista da larvicultura, o cultivo multitrófico integrado de M. amazonicum e O. niloticus não influenciou significativamente a rentabilidade quando comparado com o sistema de monocultura.

Concentrações séricas de retinol de éguas gestantes em haras do Vale do Rio Doce e Sul de Minas Gerais / Retinol serum concentration in pregnant mares in farms of Vale do Rio Doce and Sul de Minas Gerais, Brazil

Foram analisadas as concentrações séricas de retinol de 16 éguas gestantes em haras de duas diferentes regiões de Minas Gerais (Vale do Rio Doce e Sul de Minas). Os animais foram mantidos em pastagens com sal mineral à vontade, sem qualquer suplementação concentrada. Amostras de sangue foram coletadas a cada 30 dias, nos meses de maio a novembro de 2002, objetivando verificar a necessidade de suplementação das éguas com vitamina A nos meses de seca. A concentração de betacaroteno das pastagens também foi correlacionada com as concentrações sorológicas de vitamina A, a fim de verificar a utilização da reserva hepática dessa vitamina pelos eqüinos. As análises do retinol sorológico e do betacaroteno das pastagens foram realizadas por cromatografia líquida de alta eficiência (HPLC). O experimento foi em parcelas subdivididas, no delineamento inteiramente ao acaso, e os resultados foram comparados pelo teste Duncan. A correlação entre as concentrações séricas de retinol e betacaroteno das pastagens foi estimada pelo método de Pearson. Os resultados demonstraram que, no ano de 2002, não houve necessidade de suplementação das éguas dos haras das regiões estudadas nos meses de seca e que não houve correlação entre os teores de retinol plasmático das éguas com os de betacaroteno das pastagens.

Retinol serum concentrations were analyzed from 16 pregnant mares raised in farms of two different regions of Minas Gerais state, Brazil (Vale do Rio Doce and Sul de Minas). The animals were maintained on pasture with free access to mineral supplement without grain concentrate supplementation. Blood samples were collected monthly from May to November 2002, aiming to verify the need of vitamin A supplementation during the dry season. The concentration of beta-carotene from pasture samples was also correlated with blood plasma concentration to verify the utilization of hepatic stock of vitamin A. High performance liquid chromatography (HPLC) was used to determine vitamin A and beta-carotene concentrations. The used statistics was the split plot design and the results were compared by Duncan test. The Pearson correlation between the serum concentration of retinol and beta-carotene from pasture was estimated. The results demonstrated that the supplementation of pregnant mares in farms of the studied regions was not necessary during the dry season and that no significant correlation between the serum concentration of retinol and beta-carotene from pasture was observed.

Composicão química dos cascos de eqüinos das racas Pantaneira e Mangalarga Marchador / Chemical composition of black versus non-pigmented hooves from Pantaneira and Mangalarga Marchador horses

Pesquisaram-se eventuais diferencas na composicão da matéria seca (MS), proteína bruta, extrato etéreo, cinzas, cálcio, fósforo, cobre, zinco, perfil de aminoácidos e biotina entre cascos pretos e claros, de eqüinos das racas Pantaneira e Mangalarga Marchador, criados na região do Pantanal, MS, e no município de Caeté, MG, respectivamente. De cada raca foram coletadas amostras de 10 éguas vazias, não lactantes, com idade entre 5 e 10 anos, sendo que, em um mesmo animal, foram retiradas amostras das duas coloracões de casco nas regiões da pinca, ombro, quarto e talão. Na raca Pantaneira, os cascos claros apresentaram maior teor de fósforo que os pretos, e os demais elementos avaliados não foram diferentes segundo a cor. Na Mangalarga Marchador, não houve diferenca entre os cascos claros e pretos, quanto a todas as características estudadas.

Efeito do nível de óleo de milho adicionado à dieta de eqüinos sobre a digestibilidade dos nutrientes / Effect of level of corn oil in the diet of horses on the nutrient digestibilities

Avaliou-se o efeito da adição de diferentes níveis de óleo de milho sobre a digestibilidade aparente dos nutrientes da dieta de 28 eqüinos com idade e peso entre seis e 10 anos e 400 e 500kg, respectivamente. A dieta, composta de feno de coast cross(Cynodon dactylon) e ração comercial, foi oferecida na proporção de 2 por cento do peso do animal e a quantidade oferecida foi calculada a cada pesagem, sendo 50 por cento de concentrado e 50 por cento de feno. O delineamento experimental foi o inteiramente ao acaso, com quatro tratamentos e sete repetições, sendo T1, T2, T3 e T4 correspondentes à adição de 0, 250, 500, 750ml de óleo no concentrado diário ou 0, 2,9, 5,7 e 8,3 por cento de óleo na dieta total, respectivamente, e as médias foram comparadas pelo teste t de Student. A adição de óleo na dieta dos eqüinos não alterou a digestibilidade da matéria seca, proteína bruta, fibra detergente neutra e fibra detergente ácida e aumentou a digestibilidade da energia bruta e do extrato etéreo, indicando que é possível adicionar até 750ml de óleo de milho no concentrado diário dos eqüinos (8,3 por cento na dieta total) por um período de até 23 dias, visando aumentar o nível energético da dieta sem o correspondente aumento no fornecimento de matéria seca.

The two-component PhoR-PhoP system controls both primary metabolism and secondary metabolite biosynthesis in Streptomyces lividans.

The biosynthesis of most secondary metabolites in different bacteria is strongly depressed by inorganic phosphate. The two-component phoR-phoP system of Streptomyces lividans has been cloned and characterized. PhoR showed all of the characteristics of the membrane-bound sensor proteins, whereas PhoP is a member of the DNA-binding OmpR family. Deletion mutants lacking phoP or phoR-phoP, were unable to grow in minimal medium at low phosphate concentration (10 microM). Growth was fully restored by complementation with the phoR-phoP genes. Both S. lividans DeltaphoP and DeltaphoR-phoP deletion mutants were unable to synthesize extracellular alkaline phosphatase (AP) as shown by immunodetection with anti-AP antibodies and by enzymatic analysis, suggesting that the PhoR-PhoP system is required for expression of the AP gene (phoA). Synthesis of AP was restored by complementation of the deletion mutants with phoR-phoP. The biosynthesis of two secondary metabolites, actinorhodin and undecylprodigiosin, was significantly increased in both solid and liquid medium in the DeltaphoP or DeltaphoR-phoP deletion mutants. Negative phosphate control of both secondary metabolites was restored by complementation with the phoR-phoP cluster. These results prove that expression of both phoA and genes implicated in the biosynthesis of secondary metabolites in S. lividans is regulated by a mechanism involving the two-component PhoR-PhoP system.

Vasorelaxant effects of the potassium channel opener SR 47063 on the isolated human saphenous vein and rat aorta.

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1, 2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitr ochromene), a new K(+)-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1 nM to 1 microM) in the presence or absence of 3 microM glibenclamide. SR 47063 potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10 microM noradrenaline in a concentration-dependent manner, showing slightly greater activity in the aorta. The potency of the effect of SR 47063 on HSV and RA was 12- and 58-fold greater, respectively, than that reported for the structurally related K(+)-channel opener levcromakalim. The vasorelaxant action of SR 47063 in both blood vessels was strongly inhibited by 3 microM glibenclamide, consistent with a mechanism of action involving ATP-dependent K(+)-channels.

Vasorelaxant effects of the potassium channel opener SR 47063 on the isolated human saphenous vein and rat aorta

The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1,2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitrochromene), a new K+-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1 nM to 1 µM) in the presence or absence of 3 µM glibenclamide. SR 47063 potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10 µM noradrenaline in a concentration-dependent manner, showing slightly greater activity in the aorta. The potency of the effect of SR 47063 on HSV and RA was 12- and 58-fold greater, respectively, than that reported for the structurally related K+-channel opener levcromakalim. The vasorelaxant action of SR 47063 in both blood vessels was strongly inhibited by 3 µM glibenclamide, consistent with a mechanism of action involving ATP-dependent K+-channels

Actions of L-NAME and methylene blue on the hypotensive effects of clonidine and rilmenidine in the anesthetized rat.

The antihypertensive mechanism of alpha2-adrenoceptor agonists, such as clonidine and rilmenidine, is not completely elucidated, although it is probably due to reduction of sympathetic tone mediated by stimulation of central alpha2-adrenoceptors. Because activation of alpha2-adrenoceptors on endothelial cells induces release of endothelium-derived relaxing factor (EDRF), we determined whether nitric oxide (NO) release is involved in the antihypertensive action of clonidine and rilmenidine. In chloralose-anesthetised Wistar rats, systolic and diastolic arterial blood pressures were recorded on a polygraph. Intravenous injection of clonidine or rilmenidine (control group) caused a rapid increase of arterial blood pressure. followed by a long-lasting hypotensive effect. The hypotensive effects, estimated as the area enclosed by the decrease in diastolic pressure during the 20 min after clonidine and rilmenidine injections, were 574+/-60 and 410+/-59 mm Hg/min, respectively. The delta decrease in diastolic arterial blood pressure observed 20 min after intravenous injections of clonidine and rilmenidine was 48+/-5 and 34+/-3 mm Hg, respectively. Clonidine and rilmenidine injected 5-10 min after intravenous pretreatment with L-NAME (2 and 1 mg/kg) or methylene blue (10 mg/kg) induced hypotensive effects that were significantly smaller than that observed for the control group. These results suggest that the antihypertensive effects of clonidine and rilmenidine also may be modulated by the NO-cyclic guanosine monophosphate (cGMP) pathway at the level of the central nervous system and/or at the vascular peripheral circulation.

Studies on the anti-allergic activity of Mikania glomerata.

A fraction (MG1) obtained from the ethanolic extract of Mikania glomerata Sprengel (Compositae), popularly known as 'guaco' and used as 'an' anti-allergic and anti-inflammatory agent, was evaluated for these properties on ovalbumin-induced allergic pleurisy and in models of local inflammation induced by biogenic amines, carrageenan and PAF. Plasma exudation as well as neutrophil and eosinophil infiltration evoked by the intrapleural injection of the antigen were significantly reduced by the fraction. Likewise, PAF-induced pleural neutrophil migration was inhibited by the treatment with MG1. On the other hand, pre-treatment of the animals with MG1 failed to modify the pleurisy induced by histamine, serotonin or carrageenan. These results suggest that MG1 is effective in inhibiting immunologic inflammation but did not affect acute inflammatory response caused by other agents.

Purification, properties, and N-terminal amino acid sequence of a kallikrein-like enzyme from the venom of Lachesis muta rhombeata (Bushmaster).

Pit viper venoms contain multiple proteinases which cause considerable damage in tissues and systemic effects after envenomation. A proteinase, kallikrein-like enzyme, belonging to the serine group must play a very important role on systemic effects. The corresponding enzyme from Lachesis muta rhombeata venom was purified to homogeneity by a combination of isoelectrofocusing fractionation followed by one step of gel filtration HPLC. The enzyme focused with pI 5.0-6.5, it had a molecular mass of 32 kDa by gel filtration HPLC, had edematogenic activity, and induced a hypotensic effect in anesthetized rats. It exhibited strong N-alpha-tosyl-L-Arg methyl esterase (955.38 units/mg) and N-Bz-DL-Arg-pNA amidolytic (233.02 units/mg) activities, hydrolyzed tripeptide nitroanilide derivatives weakly or not at all, and cleaved selectively the A-alpha and B-beta chains of fibrinogen, apparently leaving the Y-chain unaffected. The 30 N-terminal amino acid sequence of the L. m. rhombeata protein showed greatest identity (74% in 26 amino acids) with Crotalus viridis kallikrein-like protein, but significant similarities in sequence were observed with enzymes from other snake venoms and pig pancreatic kallikrein.

Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat.

1. The effects of niflumic acid, an inhibitor of calcium-activated chloride currents, were compared with the actions of the calcium channel blocker nifedipine on noradrenaline- and 5-hydroxytryptamine (5-HT)-induced pressor responses of the rat perfused isolated mesenteric vascular bed. 2. Bolus injections of noradrenaline (1 and 10 nmol) increased the perfusion pressure in a dose-dependent manner. Nifedipine (1 microM) inhibited the increase in pressure produced by 1 nmol noradrenaline by 31 +/- 5%. Niflumic acid (10 and 30 microM) also inhibited the noradrenaline-induced increase in perfusion pressure and 30 microM niflumic acid reduced the pressor response to 1 nmol noradrenaline by 34 +/- 6%. 3. The increases in perfusion elicited by 5-HT (0.3 and 3 nmol) were reduced by niflumic acid (10 and 30 microM) in a concentration-dependent manner and 30 microM niflumic acid inhibited responses to 0.3 and 3 nmol 5-HT by, respectively, 49 +/- 8% and 50 +/- 7%. Nifedipine (1 microM) decreased the pressor response to 3 nmol 5-HT by 44 +/- 9%. 4. In the presence of a combination of 30 microM niflumic acid and 1 microM nifedipine the inhibition of the pressor effects of noradrenaline (10 nmol) and 5-HT (3 nmol) was not significantly greater than with niflumic acid (30 microM) alone. Thus the effects of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contractions induced by 5-HT (3 nmol) were not reduced by 30 microM niflumic acid, suggesting that this agent does not inhibit calcium release from the intracellular store or the binding of 5-HT to its receptor. 6. Niflumic acid 30 microM did not inhibit the pressor responses induced by KCl (20 and 60 mumol) which were markedly reduced by 1 microM nifedipine. In addition, 1 microM levcromakalim decreased pressor responses produced by 20 mumol KCl. These data suggest that niflumic acid does not block directly calcium channels or activate potassium channels. 7. It is concluded that niflumic acid selectively reduces a component of noradrenaline- and 5-HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels. Our data suggest that the Ca(2+)-activated chloride conductance may play a pivotal role in the activation of voltage-gated calcium channels in agonist-induced constriction of resistance blood vessels.

Participation of kinins in the inhibitory action of captopril on acute hypertension induced by L-NAME in anesthetized rats.

The aim of the present study was to investigate the role of bradykinin in the inhibitory action of captopril in hypertension induced by L-NAME in anesthetized rats. Male Wistar rats (260-320 g) were anesthetized with chloralose and arterial blood pressure was recorded with a polygraph pressure transducer. The hypertensive effect of L-NAME was studied in rats pretreated with saline, captopril or HOE 140 plus captopril. The effect of captopril was also studied during the sustained pressor effect of L-NAME. The acute pressor effect of L-NAME (10 mg/kg, i.v.) was significantly reduced by i.v. pretreatment with 2 mg/kg captopril (delta increase of 49 +/- 4.9 mmHg reduced to 20 +/- 5.4 mmHg, P = 0.01). The pressor effect of L-NAME (delta increase of 38 +/- 4.8 mmHg) observed in rats pretreated with captopril and HOE 140 (0.1 mg/kg, i.v.) was not significantly different from that induced by L-NAME in rats pretreated with saline (P = 0.09). During the sustained pressor effect induced by L-NAME (delta increase of 49 +/- 4.9 mmHg) captopril induced a significant (P < 0.05) reduction in arterial blood pressure (delta decrease of 22 +/- 3.0 mmHg). The present results demonstrate that the acute pressor effect of L-NAME is reduced by captopril and this inhibitory effect may be partly dependent on the potentiation of the vasodilator actions of bradykinin.

Effects of potassium channel modulators cromakalim, tetraethylammonium and glibenclamide on the contractility of the isolated human ureter.

PURPOSE: Experiments were performed to assess the effect of the potassium channel modulators cromakalim, tetraethylammonium (TEA) and glibenclamide on the contractility of isolated human ureteric rings. MATERIALS AND METHODS: Segments of human distal ureter obtained from kidney donors (leftovers) were cut into rings and suspended in an organ bath filled with modified Tyrode solution for measurement of isometric contractile force. The ureter was stimulated electrically or with KCl, and the contractile activity recorded on a polygraph. RESULTS: The amplitude of the contraction induced by electrical stimulation was not changed by glibenclamide but was enhanced by tetraethylammonium. The resting tension of the ureter was not changed by either potassium channel inhibitor. Cromakalim did not change the resting tension of the human ureter per se but induced a concentration-dependent inhibition of the contractions induced by electrical stimulation. This inhibitory effect of cromakalim was not changed by tetraethylammonium but was inhibited by glibenclamide. A phasic and tonic contractile response in the isolated human ureteric ring was induced by 60 mM. KCl. The phasic contractions were abolished by cromakalim whereas the tonic contractions were unaffected. Following sustained contraction induced by 25 mM. KCl, the cumulative addition of cromakalim to the organ bath produced a concentration-dependent relaxation. However, in rings precontracted with 60 mM. KCl, cromakalim at a concentration as high as 10(-5) M. did not induce relaxation. The cromakalim-induced relaxation of rings precontracted with 25 mM. KCl was significantly inhibited by glibenclamide. CONCLUSION: These results suggest that potassium channels are important in the control of human ureter contractility and that potassium channel openers may be an alternative therapeutic indication in the treatment of human ureteric colic.

Effect of niflumic acid on noradrenaline-induced contractions of the rat aorta.

1. The effects of niflumic acid, an inhibitor of calcium-activated chloride channels, were compared with the actions of the calcium channel antagonist nifedipine on noradrenaline-evoked contractions in isolated preparations of the rat aorta. 2. The cumulative concentration-effect curve to noradrenaline (NA) was depressed by both nifedipine and niflumic acid in a reversible and concentration-dependent manner. The degree of inhibition of the maximal contractile response to NA (1 microM) produced by 10 microM niflumic acid (38%) was similar to the effect of 1 microM nifedipine (39%). 3. Contractions to brief applications (30 s) of 1 microM NA were inhibited by 55% and 62% respectively by 10 microM niflumic acid and 1 microM nifedipine. 4. In the presence of 0.1 microM nifedipine, niflumic acid (10 microM) produced no further inhibition of the NA-evoked contractions. Thus, the actions of niflumic acid and nifedipine were not additive. 5. In Ca-free conditions the transient contraction induced by 1 microM NA was not inhibited by niflumic acid (10 microM) and therefore this agent does not reduce the amount of calcium released from the intracellular store or reduce the sensitivity of the contractile apparatus to calcium. 6. Niflumic acid 10 microM did not inhibit the contractions produced by KCl (up to 120 mM) which were totally blocked by nifedipine. Contractions induced by 25 mM KCl were completely inhibited by 1 microM levcromakalim but were unaffected by niflumic acid. 7. It was concluded that niflumic acid produces selective inhibition of a component of NA-evoked contraction which is probably mediated by voltage-gated calcium channels. These data are consistent with a model in which NA stimulates a calcium-activated chloride conductance which leads to the opening of voltage-gated calcium channels to produce contraction.

Differential vasorelaxant effects of levcromakalim and P1060 in the isolated KCl- and RbCl-precontracted human saphenous vein: possible involvement of intracellular Ca2+ stores.

The influence of rubidium-substituted physiological salt solution (Rb-PSS) on the relaxant effects of K+ channel openers was investigated in the human saphenous vein. In tissues precontracted with 20 mM KCl (in K-PSS) levcromakalim and P1060 produced complete, sustained relaxations. However, in Rb-PSS (containing 20 mM RbCl) these effects were inhibited and, although complete relaxations still occurred, were transient. When caffeine was applied at the beginning of this fade of levcromakalim-induced relaxation in Rb-PSS its contractile effect was potentiated. Similarly, the contraction to noradrenaline was potentiated when applied at the beginning of this fade of levcromakalim-induced relaxation, whereas this response was attenuated in control tissues bathed in 20 mM KCl (in K-PSS). Our results show that the relaxant effects of K+ channel openers in human saphenous vein are inhibited in Rb-PSS, in agreement with previous studies in animal tissue, and suggest that an increased Ca2+ uptake into intracellular stores may be contributory to vasorelaxation.