Made available in DSpace on 2014-06-11T19:22:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-18Bitstream added on 2014-06-13T20:08:35Z : No. of bitstreams: 1 freitas_scl_me_ilha.pdf: 1038067 bytes, checksum: de418f750a6f2441df99083abd72c137 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O acelerado desenvolvimento da eletrônica de potência vem desencadeando uma série de transformações no sistema elétrico, sendo possível destacar a constante alteração da natureza das cargas consumidoras, a proliferação da co-geração e o peso crescente de questões ambientais relacionadas à questão da geração. Grande parte das cargas atuais é composta por dispositivos não-lineares que, por muitas vezes, são a causa de problemas relacionados à qualidade da energia elétrica. Considerando a variedade da distribuição sequencial das harmônicas de corrente na utilização dos filtros passivos, destacam-se os filtros e bloqueadores eletromagnéticos, os quais têm merecido especial atenção devido à sua robustez e baixo custo de implantação. Este trabalho está particularmente direcionado à investigações relacionadas ao uso desses dispositivos que possibilitam uma atenuação do fluxo das principais componentes harmônicas que compõe as distorções harmônicas de sequência zero. Neste contexto, esta dissertação apresenta contribuições inéditas relacionadas com o desenvolvimento de modelos matemáticos no domínio da frequência para bloqueadores eletromagnéticos, e um estudo de modelos matemáticos para filtros eletromagnéticos, compondo então, o aqui denominado supressor eletromagnético de componentes de sequência zero. Apresenta-se ainda, a utilização de metodologias para análise de desempenho baseado no comportamento das componentes harmônicas sequenciais. É estabelecida uma base comparativa de natureza experimental que possibilita a avaliação do desempenho e da aderência do modelo proposto. São utilizados protótipos de baixa potência de um filtro e um bloqueador, ambos eletromagnéticos, construídos a partir de análises teóricas. Os modelos desenvolvidos são utilizados na composição de um aplicativo computacional para análise... / The accelerated development of power electronics has promoted a series of changes in the electrical system, so it is possible to highlight the constant changing of consumer loads, the proliferation of co-generation and the growing importance of environmental issues related to generation. Much of the current loads are composed of non-linear devices which, in many cases are the cause of problems related to power quality. Considering the sequential distribution variety of harmonic currents in the use of passive filters, highlight the electromagnetic filters and blockers, which have received special attention due to its robustness and low cost of deployment. This work is particularly directed to investigations related to the use of these devices which enable an attenuation of the flow of the principal harmonic components that compound the zero-sequence harmonic distortion. In this context, this work presents unedited contributions related to the development of mathematical models in the frequency domain for electromagnetic blocking, and a study of mathematical models of electromagnetic filters, making then, the here called electromagnetic zero-sequence components suppressor. It presents also, the use of methodologies for performance analysis based on the sequential behavior of harmonic components. It is established a comparison basis of experimental nature that enables the performance and adherence analysis of the model. Are used a low-power prototypes of a filter and a blocker, both electromagnetic, constructed from theoretical analysis. These models are used in the composition of a software for performance analysis and optimal project of harmonic filtering systems. This tool allows an individualized and systematic investigation of the electrical system behavior for distinct harmonic sequence components. Thus, through a detailed investigation it is possible to identify appropriated actions... (Complete abstract click electronic access below)

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Das EKG ist ein etabliertes und einfach durchzuführendes diagnostisches Routineverfahren. Belastungsuntersuchungen in denen das EKG beispielsweise Aufschluss über myokardiale Ischämien und Rhythmusstörungen geben kann, belegen den hohen diagnostischen Stellenwert des EKGs. Die Veränderungen der Parameter des EKGs sind charakteristisch und unterliegen dabei den unterschiedlichen physiologischen Bedingungen. Die vorliegende prospektive klinische Untersuchung beschäftigt sich mit der Fragestellung, welche physiologischen Bedingungen für diese Veränderungen ursächlich verantwortlich sind. Dazu wurden 10 männliche Probanden in 2 doppelten Stufen- und 2 Dauertests mit und ohne ß-Blockade untersucht. Es konnte festgestellt werden, dass in Ruhe und bei intensiver Belastung die ß-Blockade eine Wirkung hatte, was auf einen relevanten Einfluss des Sympathikus schließen lässt. Bei leichter und mittlerer Belastung und in der unmittelbaren Nachbelastungsphase waren hingegen keine Unterschiede in den Tests ohne und mit ß-Blockade festzustellen. Deshalb ist die Annahme plausibel, dass die Regulation der Herzfunktionen durch den Parasympathikus stattfindet, während der Sympathikus hier lediglich eine ergänzende Modulationsfunktion hat. Grundsätzlich unterstützt dies insgesamt die Theorie der zentralen Mitinnervation, die nach den vorliegenden Ergebnissen allerdings vorrangig in der Bedeutung des Parasympathikus und nachrangig in der des Sympathikus liegt.

Background: Surgical stress during resection surgery for colon cancer has previously been shown to be associated with adverse postoperative outcomes. Statin and beta-blocker treatment have been shown to lower postoperative complications and mortality, and been hypothesized to reduce the surgical stress response, although this correlation has not been studied clinically. Aim: To investigate whether perioperative beta-blocker and/or statin treatment reduce the postoperative C-reactive protein (CRP) response. Material and methods: All patients who underwent right sided hemicolectomy or sigmoid resection for cancer at Örebro University Hospital during 2012-2017 were included in this study. Initially, any treatment with statins, beta-blockers or both were compared to those with no treatment. After initial analyses, four treatment groups were compared regarding postoperative CRP response, namely no treatment, statin, beta-blocker, and combination treatment. Comparisons regarding complications were also performed for the four groups. Results: A total of 260 patients were included in this study. The no treatment group had a lower peak postoperative CRP than the treatment group, when comparing any treatment versus no treatment. There were no significant differences in postoperative CRP within the four treatment groups. There was no significant difference in complication rate between any of the treatment groups when compared to no treatment. Conclusion: Treatment with statin or beta-blocker therapy does not reduce the postoperative CRP response. A combination of both treatments demonstrated a trend towards a reduction regarding postoperative CRP response compared with the two treatments individually assessed. Larger studies are needed to verify the results of this study.

<p>Mosquitoes pose significant threats to human health because they act as vectors for disease causing viruses and protozoans. Indeed, <em>Aedes aegypti</em> is known as the Yellow Fever Mosquito because of its role as a vector for viral infections that kill thousands of people each year. A more thorough understanding of mosquito physiology will aid development of novel control strategies. Previous work on ion transport across the midgut has been focused primarily on larval <em>A. aegypti</em>, while research on the midgut of the adult stage is less complete. The posterior midgut of the adult female is of particular interest because it is used for the storage and digestion of the blood meal which is required for the production of eggs. This study used an array of electrophysiological methodologies such as the Scanning Ion Electrode Technique (SIET) in order to elucidate the patterns and mechanisms of Na⁺, H⁺ and K⁺ transport across the posterior midgut at intervals during postprandial diuresis and digestion of the blood meal. Measurements of transepithelial potential indicated that the lumen was at its most negative (-13.2 mV) three hours after the blood meal and then gradually became less negative during the time course of digestion. Na⁺ was absorbed (from lumen to bath) at all intervals after the blood meal (6 min, 30 min, 2h, 24 h); calculations of the electrochemical potential indicated that absorption required active transport. H⁺ absorption at all times (6 min – 48 h) after the blood meal was also active (<em>i.e.</em> against the electrochemical gradient for H⁺) and was greatly reduced by inhibition of carbonic anhydrase. K⁺ transport across the midgut exhibited two distinct phases. During diuresis, luminal concentrations of K⁺ were in the range 24 – 28 mM and secretion into the midgut was opposed by the electrochemical gradient, indicating active transport. After diuresis, during blood meal digestion, concentrations of K⁺ in the midgut contents were high (95 – 134 mM) and absorption of K⁺ was favoured by the electrochemical gradient. K⁺ absorption was sensitive to the channel blocker Ba²⁺ during this period.</p> / Master of Science (MSc)

Background: Insulin resistance may play a pathogenic role in cardiovascular disease (CVD). Resistance to insulin has been associated with obesity, hypertension, and abnormal glucose and lipid metabolism. The constellation of these features among insulin resistant subjects has been called the metabolic syndrome. Prevalence of the metabolic syndrome increases with age and is most common in the elderly. Different criteria have been proposed to define the metabolic syndrome (ATP, WHO, AACE, EGIR). Current management of metabolic syndrome focuses on the specific risk factors that the patient may have without targeting the underlying insulin resistance. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are widely used antihypertensive medications that may improve insulin sensitivity. We hypothesize that they can be used to reduce the long term cardiovascular complications in elderly hypertensive subjects with evidence of insulin resistance. In this study, we determined the effect of ACEI/ARB on the long term development of CVD in hypertensive non-diabetic elderly patients with the metabolic syndrome, as well as in patients with insulin resistance. Methods: Our research project utilizes the Cardiovascular Health Study (CHS) dataset. This dataset is a community based observational study where elderly participants were randomly selected and followed up for 11 years and the time to any cardiovascular event was recorded. In our project, we included hypertensive, non-diabetic individuals, with evidence of metabolic syndrome or insulin resistance, but had not experienced cardiovascular events at baseline. Cox regression model was used to evaluate the effect of ACEI/ARB on the time to the first cardiovascular event compared to the other antihypertensive medications adjusting for possible confounders such as age, race, gender, smoking status, triglycerides, LDL levels, systolic blood pressure, development of diabetes, congestive heart failure (CHF) and the number of anti-hypertensives. Results: In elderly hypertensive non-diabetic subjects with the metabolic syndrome according to the ATP and the WHO criteria, the hazard ratio for CVD associated with the use of ACEI/ARB was 0.65 or 0.68 (with 95 % C.I. of [0.45, 0.98], and [0.48, 0.96]) respectively when compared to the group exposed to the other anti-hypertensives. When the metabolic syndrome was defined according to the AACE and EGIR, the use of ACE/ARB was associated with hazard ratios for CVD equal to 0.74 and 0.899, respectively (with 95 % C.I. of [0.54, 1.09] and [0.61, 1.34]) compared to the use of the other anti-hypertensives. Hypertensive non-diabetic elderly subjects who were insulin resistant as evidenced by a HOMA-IR in the upper quartile, had a hazard ratio for CVD of 0.78 (95 % C.I. [0.56, 1.09]) associated with the use of ACEI/ARB compared to the use of other anti-hypertensives. Conclusions: The effect of ACEI/ARB on the development of cardiovascular events differs according to the definition of the metabolic syndrome. Elderly hypertensive patients with the metabolic syndrome, defined by ATP and WHO, seem to have lower risk of CVD with ACEI/ARB compared to the other antihypertensive medications. However, this association is not significant in elderly hypertensive patients in the upper quartile of HOMA and in patients with the metabolic syndrome as defined by AACE and EGIR criteria.

The Two-pore channel (TPC1-3) family represents a recently identified class of endolysosomal ion channels. TPCs were originally proposed to be promising candidate channels for NAADP-induced Ca²⁺ release. However, subsequent studies have emerged to propose an alternative view where TPCs may be Na+-selective channels regulated by the lysosome-specific phosphoinositide PI(3,5)P2 or voltage in an isoform-dependent manner. This thesis asks the question of whether pharmacological and ion permeation properties of TPCs, in particular the human TPC2, may satisfy or may be consistent with the requirement of a potential NAADP-sensitive Ca²⁺-release channel. These fundamental properties of hTPC2 were approached using patch-clamp electrophysiology and confocal fluorescence microscopy, and were analysed quantitatively to extract relevant physical parameters important to our understanding of their physiological and functional significance. Chapter 2 presents the basic electrophysiological characterisation of hTPC2. It follows a logical way by first determining the ion permeation properties, followed by the investigation of its physical relation with fractional Ca²⁺ current and Ca²⁺ nanodomains to rigorously prove that this Na⁺ selectivity is sufficient to ensure negligible Ca²⁺ leakage both experimentally and theoretically. This follows the logic that matter must not be created nor destroyed so that a Na+-selective channel that poses a physiologically significant energy barrier to Ca²⁺ permeation from one side would not lead to the creation of Ca²⁺ on the other side. Chapter 3 represents a natural progression from Chapter 2 and is aimed at investigating the underlying mechanisms responsible for the electrophysiological ion selectivity observed. This chapter also follows a logical way by first identifying spermine as a high valence intracellular blocker, its mutual antagonism with different external ionic species that allows the determination of ion-binding affinity, followed by the determination of the concentration dependence of ion conduction to identify possible lower affinity binding. By considering all the above qualities, the outcome is a coherent description and connection of ion binding selectivity, kinetic selectivity and ion binding configuration with the observed electrophysiological selectivity. Chapter 4 discusses the missing puzzles and how these questions might be addressed.

The quest for multi-standard and software-defined radio (SDR) receivers calls for high flexibility in the receiver building-blocks so that to accommodate several wireless services using a single receiver chain in mobile handsets. A potential approach to achieve flexibility in the receiver is to move the analog-to-digital converter (ADC) closer to the antenna so that to exploit the enormous advances in digital signal processing, in terms of technology scaling, speed, and programmability. In this context, continuous-time (CT) delta-sigma (ΔƩ) ADCs show up as an attractive option. CT ΔƩ ADCs have gained significant attention in wideband receivers, owing to their amenability to operate at a higher-speed with lower power consumption compared to discrete-time (DT) implementations, inherent anti-aliasing, and robustness to sampling errors in the loop quantizer. However, as the ADC moves closer to the antenna, several blockers and interferers are present at the ADC input. Thus, it is important to investigate the sensitivities of CT ΔƩ ADCs to out-of-band (OOB) blockers and find the design considerations and solutions needed to maintain the performance of CT ΔƩ modulators in presence of OOB blockers. Also, CT ΔƩ modulators suffer from a critical limitation due to their high sensitivity to the clock-jitter in the feedback digital-to-analog converter (DAC) sampling-clock. In this context, the research work presented in this thesis is divided into two main parts. First, the effects of OOB blockers on the performance of CT ΔƩ modulators are investigated and analyzed through a detailed study. A potential solution is proposed to alleviate the effect of noise folding caused by intermodulation between OOB blockers and shaped quantization noise at the modulator input stage through current-mode integration. Second, a novel DAC solution that achieves tolerance to pulse-width jitter by spectrally shaping the jitter induced errors is presented. This jitter-tolerant DAC doesn’t add extra requirements on the slew-rate or the gain-bandwidth product of the loop filter amplifiers. The proposed DAC was implemented in a 90nm CMOS prototype chip and provided a measured attenuation for in-band jitter induced noise by 26.7dB and in-band DAC noise by 5dB, compared to conventional current-steering DAC, and consumes 719µwatts from 1.3V supply.

Made available in DSpace on 2015-05-14T12:59:25Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1262940 bytes, checksum: 3eb5eef404a585e59e9d6b96edc0609c (MD5) Previous issue date: 2011-02-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The pharmacological effects induced by CH2Cl2/MeOH extract (EDP) and Hexane/EtOAc phase (FDP) from the Brazilian alga Dictyota pulchella were studied on the cardiovascular system of Wistar rats using a combined in vivo and in vitro approach. All protocols in this study were approved by the CEPA/LTF (protocol nº 0208/10). In normotensive conscious male rats, EDP injections (5; 10; 20 and 40 mg/kg, i.v., randomly) produced hypotension (-4.1 ± 1.34; -7.0 ± 2.4; -46.9 ± 1.3 and - 54.8 ± 4.3%; respectively) and bradycardia (-2.1 ± 1.6; -4.0 ± 2.3; -66.8 ± 5.2 and - 74.7 ± 4.5%; respectively) (n=5). Isolated superior mesenteric artery rings (1-2 mm) were suspended by cotton threads for isometric tension recordings in a Tyrode s solution at 37 ºC, gassed with a 95% O2 and 5% CO2, under a resting tension of 0.75g. In phenylephrine (Phe, 1&#956;M)-pre-contracted rings, EDP (0.01 500 &#956;g/mL) induced a concentration-dependent relaxation (Maximum Response = 101.4 ± 4.5%; EC50 = 22.35 ± 5.09 &#956;g/mL) and this effect was not modified by removal of the vascular endothelium (MR = 103.3 ± 8.3%; EC50 = 21.43 ± 8.98 &#956;g/mL, n=7). Similar results were found in the presence of FDP (0.01 500 &#956;g/mL). FDP induced a concentration-dependent vasodilatation in both endothelium-intact (MR = 80.6 ± 5.8%; EC50 = 24.1 ± 8.95 &#956;g/mL, n=6) or endothelium-denuded mesenteric artery rings (MR = 95.6 ± 7.5%; EC50 = 23.7 ± 5.65 &#956;g/mL, n=6). Based on the preliminary results, the subsequent experiments were performed in rings without endothelium. To appreciate the involvement of potassium channels, the preparations were preincubated with Tyrode s modified solution, KCl (20 mM) or with non-selective K+ channel blocker, tetraethylammonium (TEA, 3 mM). In both preparations the vasorelaxant activity was not changed. In the presence of a tromboxane A2 agonist U-46619 (100 nM), EDP induced concentration-dependent vasodilatation (MR = 90.3 ± 7.8%; EC50 = 24.63 ± 4.04 &#956;g/mL, n=6) was similar to the response found under Phe-induced. After exposure to high concentrations of extracellular K+ (KCl, 60 mM), the EDP induced concentration-dependent vasodilatation (MR = 97.7 ± 4.0%; EC50 = 34.57 ± 5.11 mg/mL; n=6). In the same experimental condition, FDP induced concentration-dependent vasodilatation (MR = 113.5 ± 6.1%; EC50 = 10.92 ± 2.81 &#956;g/mL; n=6). This result indicates that both EDP and FDP act on voltage-operated calcium channel (Cav). Furthermore, EDP and FDP (0.03; 0.3; 10; 30 e 100 &#956;g/mL) antagonized CaCl2-induced contractions. The extract also induced vasodilatation in the contraction evoked by L-type Ca2+ channel agonist (Bay K 8644, 200 nM) (MR = 113.3 ± 6.7%; EC50 = 19.45 ± 6.66 &#956;g/mL, n=7). These results suggest that EDP induces hypotension and bradycardia. Both EDP and FDP induce endotheliumindependent vasodilatation that involves the inhibition of the Ca2+ influx through blockade of Cav. / Os efeitos farmacológicos do extrato CH2Cl2:MeOH (EDP) e fase Hexano:AcOEt (FDP) da alga marinha brasileira Dictyota pulchella foram estudados sobre o sistema cardiovascular de ratos, utilizando uma abordagem in vivo e in vitro. Em ratos normotensos não anestesiados, EDP (5; 10; 20 e 40 mg/kg, i.v., randomicamente) promoveu hipotensão (-4,1 ± 1,34; -7,0 ± 2,4; -46,9 ± 1,3 e -54,8 ± 4,3%, respectivamente) acompanhada de bradicardia (-2,1 ± 1,6; -4,0 ± 2,3; -66,8 ± 5,2 e - 74,7 ± 4,5%, respectivamente) (n=5). Em anéis de artéria mesentérica superior isolada de rato pré-contraídos com Fenilefrina (FEN) 1 &#956;M, EDP (0,01 500 &#956;g/mL) promoveu um efeito vasorrelaxante dependente de concentração na presença do endotélio vascular (Emáx = 101,4 ± 4,5%; CE50 = 22,35 ± 5,09 &#956;g/mL), e este efeito não foi alterado após a remoção do endotélio (Emáx = 103,3 ± 8,3%; CE50 = 21,43 ± 8,98 &#956;g/mL) (n=7). Resultados semelhantes foram obtidos na presença de FDP (0,01 500 &#956;g/mL), observando-se um vasorrelaxamento tanto na presença (Emáx = 80,6 ± 5,8%; CE50 = 24,1 ± 8,9 &#956;g/mL), quanto na ausência do endotélio funcional (Emáx = 95,6 ± 7,5%; CE50 = 23,70 ± 5,65 mg/mL). Para avaliar se o efeito de EDP era dependente do tônus vascular, este extrato foi testado no tônus basal, na presença ou ausência do endotélio, demonstrando que a resposta não foi alterada em nenhuma das duas situações. Baseado nos resultados preliminares, os experimentos subseqüentes foram realizados com endotélio desnudo. Para avaliar a participação dos canais para potássio (K+), utilizou-se uma solução com 20 mM de KCl ou tetraetilâmonio (TEA) 3 mM. Em ambas as preparações (Emáx = 102,3 ± 4,8%; CE50 = 25,40 ± 6,05 &#956;g/mL) ou (Emáx = 111,2 ± 5,3%; CE50 = 16,70 ± 3,61 &#956;g/mL) (n=7), respectivamente, a atividade vasorrelaxante de EDP não foi alterada. Na presença de outro agente contracturante, U46619 (100 nM), EDP promoveu um efeito vasorrelaxante (Emáx = 90,3 ± 7,8%; CE50 = 24,63 ± 4,04 &#956;g/mL) de maneira similar aos anéis pré-contraídos com FEN. Em experimentos contendo uma solução despolarizante de 60 mM de KCl, EDP causou vasorrelaxamento dependente de concentração (Emáx = 97,7 ± 4,0%; CE50 = 34,57 ± 5,11 mg/mL; n=6). Na mesma condição experimental, FDP também promoveu um efeito vasorrelaxante (Emáx = 113,5 ± 6,1%; CE50 = 10,92 ± 2,81 &#956;g/mL; n=6), não havendo diferença significante, para os dois compostos, quando comparados aos anéis pré-contraídos com FEN. Sugere-se que tanto EDP quanto FDP atuem sobre os canais para cálcio sensíveis a voltagem (Cav). Além disso, EDP e FDP (0,03; 0,3; 10; 30 e 100 &#956;g/mL) antagonizaram as contrações induzidas por CaCl2. O extrato ainda produziu vasorrelaxamento na presença de um agonista de canais para Ca2+ tipo-L (Bay K 8644; 200 nM) (Emáx = 113,3 ± 6,7% e CE50 = 19,45 ± 6,66 &#956;g/mL, n=7). Esses resultados sugerem que EDP produz hipotensão e bradicardia transientes, e tanto EDP quanto FDP promovem vasorrelaxamento independente do endotélio vascular por inibição do influxo de Ca2+, por meio do bloqueio dos Cav.

Made available in DSpace on 2015-05-14T12:59:27Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2410324 bytes, checksum: 683a4ac95271e3c06063aa05abced89b (MD5) Previous issue date: 2011-03-25 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The genus Lippia (Verbenaceae) has yielded a great number of medicinal and economically important species that are frequently used in folk medicine for treatment of several diseases, such as: coughs, bronchitis, liver disorders and hypertension. L. microphylla Cham. is a plant of the genus Lippia found in the Northeast of Brazil, and there is no information in the literature concerning its cardiovascular effects. Therefore, this study aimed to evaluate the cardiovascular effects of the essential oil of L. microphylla Cham. (EOLM) and of its main constituent, thymol. In normotensive non-anaesthetized rats, EOLM injections produced hypotension (ED50=5.5 (4.1-7.3) mg/Kg, n=5) and bradycardia (ED50=5.2 (4.3-6.2) mg/Kg, n=5). Isometric tension recordings revealed that EOLM (1 300 μg/mL) caused concentration-dependent relaxation in isolated mesenteric rings, with functional endothelium, pre-contracted with phenylephrine (10 μM) (EC50=28.2 (25.3-31.4) μg/mL, n=5) and this effect was not attenuated by removal of the vascular endothelia layer. In preparations without endothelium, pre-incubated with KCl 20 mM, the relaxantion was not changed. Furthermore, EOLM caused relaxation in mesenteric rings pre-contracted with KCl 60 mM and inhibited Ca2+ -induced vasoconstriction in a concentration-dependent manner. In addition, EOLM relaxed the contractions elicited by the L-type Ca2+ channel activator, S(-)-Bay K 8644, indicating that the vasodilatation is related to the inhibition of Ca2+ influx through L-type Ca2+ channels. To confirm this hypothesis, whole-cell L-type Ca2+ currents were recorded in freshly dispersed rat mesenteric artery myocytes. EOLM (1-100 μg/mL) significantly inhibited Ba2+ currents in a concentration-dependent manner (EC50=11.9 (9.4-15.0) μg/mL, n=4).These results suggest that OELM induce vasorelaxant effect in rat mesenteric artery due to the inhibition of the Ca2+ influx via voltage-dependent L-type Ca2+ channels. Interestingly, the relaxantion induced by thymol (EC50=9.3 (8.3-10.4) μg/mL, n=5, p<0.01) was more potent than that observed to EOLM (EC50=23.9 (22.0-26.0) μg/mL, n=5), indicating that the vascular actions of EOLM could be attributed to its main constituent, thymol. The cardiovascular responses evoked by thymol were investigated in SHR and WKY rats. In SHR and WKY non-anaesthetized rats, intravenous administration of thymol (0.1; 0.3; 1; 3; 6; 12 and 15 mg/Kg, i.v.) produced hypotension and bradycardia in a dose-dependent manner. Isometric tension recordings, the pharmacological profile of arterial relaxant effects of thymol was compared in rings of mesenteric arteries and aorta from SHR and WKY. In preparations without endothelium, thymol (1 μM 1 mM) produced relaxation in mesenteric arteries from SHR (pD2=4.40.04, n=5) and WKY (pD2=4.30.02, n=5) and aorta from SHR (pD2 = 4.40.03, n=5) and WKY (pD2=4.30.03, n=5) and this effect was not altered in preparations with functional endothelium. Furthermore, thymol relaxed the vasoconstriction induced by high K+ solution, U46619 and S(-)-Bay K 8644 in mesenteric arteries and aorta from SHR and WKY. The addition of thymol also inhibited Ca2+ -induced vasoconstriction in a concentration-dependent manner in mesenteric and aorta segments from SHR and WKY. In electrophysiological recordings, L-type Ca2+ current (ICa,L) was decreased by thymol in a concentration-dependent manner in cardiomyocytes isolated from SHR (pD2=3.40.06, n=4, p<0.05) and WKY (pD2=4.70.05, n=4). In addition, thymol lowed-down both the fast and slow time constants for L-type Ca2+ current inactivation. In conclusion, these results suggest that the vascular effects induced by EOLM and thymol are probably due to the inhibition of the Ca2+ influx via voltage-dependent L-type Ca2+ channels. / O gênero Lippia (Verbenaceae) contém um grande número de espécies medicinais e economicamente importantes, que são frequentemente utilizadas na medicina popular para o tratamento de várias doenças, tais como: tosse, bronquite, disordens hepáticas e hipertensão. L. microphylla Cham. é uma espécie do gênero Lippia encontrada no Nordeste brasileiro e não há informações na literatura a respeito de suas ações cardiovasculares. Portanto, o presente trabalho tem como objetivo avaliar os efeitos cardiovasculares do óleo essencial de L. microphylla Cham (OELM) e seu constituinte principal, o timol. Em ratos normotensos não-anestesiados, OELM produziu hipotensão (DE50=5,5 (4,1-7,3) mg/Kg, n=5) e bradicardia (DE50=5,2 (4,3-6,2) mg/Kg, n=5). Experimentos de tensão isométrica revelaram que o OELM (1 300 μg/mL) promove relaxamento dependente de concentração em anéis mesentéricos, com endotélio funcional, pré-contraídos com fenilefrina (10 μM) (EC50=28,2 (25,3-31,4) μg/mL, n=5), e este efeito não foi atenuado pela remoção do endotélio vascular. Em preparações pré-incubadas com KCl 20 mM, o relaxamento do OELM não foi alterada. Além disso, o OELM promoveu relaxamento em anéis mesentéricos pré-contraídos com KCl 60 mM e inibiu a vasoconstrição indizuda pelo Ca2+ de maneira dependente de concentração. O OELM relaxou as contrações induzidas pelo ativador de canais para Ca2+ tipo-L, o S(-)-Bay K 8644, indicando que a vasodilatação induzida pelo OELM está relacionada com a inibição do influxo de Ca2+ via canais para Ca2+ tipo-L. Para confirmar esta hipótese, correntes macroscópicas de Ca2+ foram registradas em miócitos de artéria mesentérica recém dispersas. O OELM (1 100 μg/mL) inibiu significantemente as correntes de Ba2+ de maneira dependente de concentração (CE50=11,9 (9,4-15,0) μg/mL, n=4). Estes resultados surgerem que o OELM induz efeito relaxante em artéria mesentérica de rato devido à inibição do influxo de Ca2+ via canais para Ca2+ dependente de voltage tipo-L. Interessantemente, o efeito relaxante induzido pelo timol (CE50=9,3 (8,3-10,4) μg/mL, n=5, p<0,01) foi mais potente do que o induzido pelo OELM (CE50=23,9 (22,0-26,0) μg/mL, n=5), indicando que os efeitos vasculares do OELM são provavelmente atribuídos ao seu principal constituinte, o timol. A partir dessas premissas, os efeitos cardiovasculares induzidos pelo timol foram investigados em ratos SHR e WKY. Em ratos SHR e WKY não-anestesiados, a administração intravenosa de timol (0,1; 0,3; 1; 3; 6; 12 e 15 mg/kg, i.v.) produziu hipotensão e bradicardia de maneira depedente de dose. Em experimentos de tensão isométrica, o perfil do efeito relaxante induzido pelo timol foi comparado entre artéria mesentérica e aorta isoladas de ratos SHR e WKY. Em preparações sem endotélio vascular, o timol (1 μM 1 mM) induziu relaxamento de maneira concentração dependente em artéria mesentérica isolada de SHR (pD2=4,40,04, n=5) e WKY (pD2=4,30,02, n=5) e aorta de SHR (pD2=4,40,04, n=5) e WKY (pD2=4,30,03, n=5) e este efeito não foi alterado em preparações com o endotélio. Além disso, o timol relaxou as contrações induzidas por KCl, U46619 e S(-)-Bay K 8644 em artéria mesentérica e aorta de ratos SHR e WKY. A adição do timol inibiu a vasoconstrição induzida por Ca2+ em anéis de artéria mesentérica e aorta de ratos SHR e WKY. O timol diminuiu as correntes de Ca2+ tipo-L de maneira concentração dependente em cardiomiócitos de SHR (pD2=3,40,06, n=4, p<0,05) e WKY (pD2=4,70,05, n=4). Além disso, o timol diminuiu a constante de tempo rápida e lenta para inativação das correntes de Ca2+. Em conclusão, estes resultados surgerem que os efeitos cardiovasculares induzidos pelo o OELM e timol são provavelmete devido a inibição do influxo de Ca2+ via canais para Ca2+ dependentes de voltage tipo-L.