Beauty or function? The opposing effects of natural and sexual selection on cuticular hydrocarbons in male black field crickets.

Although many theoretical models of male sexual trait evolution assume that sexual selection is countered by natural selection, direct empirical tests of this assumption are relatively uncommon. Cuticular hydrocarbons (CHCs) are known to play an important role not only in restricting evaporative water loss but also in sexual signalling in most terrestrial arthropods. Insects adjusting their CHC layer for optimal desiccation resistance is often thought to come at the expense of successful sexual attraction, suggesting that natural and sexual selection are in opposition for this trait. In this study, we sampled the CHCs of male black field crickets (Teleogryllus commodus) using solid-phase microextraction and then either measured their evaporative water loss or mating success. We then used multivariate selection analysis to quantify the strength and form of natural and sexual selection targeting male CHCs. Both natural and sexual selection imposed significant linear and stabilizing selection on male CHCs, although for very different combinations. Natural selection largely favoured an increase in the total abundance of CHCs, especially those with a longer chain length. In contrast, mating success peaked at a lower total abundance of CHCs and declined as CHC abundance increased. However, mating success did improve with an increase in a number of specific CHC components that also increased evaporative water loss. Importantly, this resulted in the combination of male CHCs favoured by natural selection and sexual selection being strongly opposing. Our findings suggest that the balance between natural and sexual selection is likely to play an important role in the evolution of male CHCs in T. commodus and may help explain why CHCs are so divergent across populations and species.

Comparación del consumo alimentario y calidad de vida relacionada con la salud entre baloncestistas de distinto nivel competitivo / Comparison of food consumption and health-related quality of life amongbasketball players of different competitive levels

Introducción: Los hábitos alimentarios y la salud mental son aspectos fundamentales para optimizar la preparación y el rendimiento deportivo de los baloncestistas.Objetivo: Comparar la frecuencia en el consumo de alimentos y la calidad de vida relacionada con la salud (CVRS)entre baloncestistas de distinto nivel competitivo (profesional,universitario y amateur). Material y métodos: Estudio transversal que evaluó 122baloncestistas masculinos (edad media de 30,60 ± 10,79años), distribuidos en jugadores de baloncesto profesional(JBP; n=25), universitario (JBU; n=26) y amateur (JBA;n=71). Las variables de estudio se evaluaron a través de encuestas en línea referentes a la frecuencia en el consumo de alimentos y CVRS (SF-36). Resultados: Los JBP ostentan un consumo significativamente mayor de cena (F= 5,007; p= 0,020) comparados conlos JBU, y de frutas (F= 5,857; p= 0,012), verduras (F= 3,756; p= 0,020) y cena (F= 5,007; p= 0,011) respecto a losJBA. Mientras que los JBU presentan un consumo significativamente mayor de frutas (F= 5,857; p= 0,035) que los JBA.Además, los JBU presentaron un consumo significativamente mayor de bebidas azucaradas (F= 9,293; p= 0,004) respecto a los JBP y JBA. La CVRS no presentó diferencias significativas entre los grupos. Conclusión: Los JBP presentan mayor frecuencia en el consumo de alimentos saludables al compararlos con JBU yJBA. Además, los JBU reportan mayor frecuencia en el consumo de bebidas azucaradas respecto a JBP y JBA. Mientras que, la CVRS es positiva independiente al nivel competitivo delos baloncestistas.(AU)

Introduction: Eating habits and mental health are fundamental aspects to optimize the preparation and sports performance of basketball players.Aim: To compare the frequency of food consumption andhealth-related quality of life (HRQoL) among basketball players of different competitive levels (professional, university,and amateur).Material and methods: Cross-sectional study that evaluated 122 male basketball players (mean age of 30.60 ± 10.79years), divided into professional (JBP; n=25), university (JBU;n=26) and amateur (JBA; n=71). The study variables wereevaluated through online surveys regarding the frequency offood consumption and HRQoL (SF-36). Results: The JBP show a significantly higher consumption of dinner (F= 5,007; p= 0,020) compared to the JBU,and of fruits (F= 5,857; p= 0,012), vegetables (F= 3,756;p= 0,020) and dinner (F= 5,007; p= 0,011) compared tothe JBA. While the JBU present a significantly higher con-sumption of fruits (F= 5,857; p= 0,035) than the JBA. In addition, the JBU had a significantly higher consumption ofsugary drinks (F= 9,293; p= 0,004) compared to the JBPand JBA. The HRQoL did not present significant differencesbetween the groups.Conclusion: The JBP have a higher frequency in the consumption of healthy foods when compared to JBU and JBA. Inaddition, the JBU report a higher frequency in the consumption of sugary drinks compared to the JBP and JBA. While, theHRQoL is positive regardless of the competitive level of thebasketball players.

Ovarian apoptosis is regulated by carbohydrate intake but not by protein intake in speckled cockroaches.

When the likelihood of reproducing successfully is low, any prior investment in developing oocytes may be wasted. One means of recouping this investment is oosorption - where ova are absorbed and resources salvaged so they can be re-allocated to other traits. Food-limited female speckled cockroaches (Nauphoeta cinerea) appear to use this strategy. However, it is unclear if total food intake or the availability of specific nutrients induces this process. Here, we used the geometric framework of nutrition to determine how protein, carbohydrate and energy intake affect levels of ovarian apoptosis and necrosis (controlled versus uncontrolled cell death) in the terminal oocytes of female N. cinerea. We then compare the effects of nutrient intake on apoptosis (a key step towards oosorption) and offspring production to better understand the relationship between diet, apoptosis and female fitness. We found that even when food was abundant, females experienced high levels of apoptosis if their diet lacked carbohydrate. Necrosis was reduced when energy intake was high, but largely irrespective of nutrient ratio. Offspring production peaked on a low protein, high carbohydrate nutrient ratio (1P:7.96C), similar to that which minimized apoptosis (1P:7.34C) but not in the region of nutrient space that minimized necrosis. Thus, females consuming an ideal nutrient blend for reproduction can invest heavily in their current brood without needing to salvage nutrients from developing ova. However, offspring production was more dependent on carbohydrate consumption than apoptosis was, suggesting that the importance of carbohydrate in reproduction goes beyond regulating oosorption. This reliance on carbohydrate for female reproduction may reflect the unusual reproductive and nutritional physiology of speckled cockroaches; attributes that make this species an exciting model for understanding how diet regulates reproduction.

Probabilistic Assessment of the Dynamic Viscosity of Self-Compacting Steel-Fiber Reinforced Concrete through a Micromechanical Model.

This article develops a probabilistic approach to a micromechanical model to calculate the dynamic viscosity in self-compacting steel-fiber reinforced concrete (SCSFRC), which implies a paradigm shift in the approach of the deterministic models used. It builds on a previous work by the authors in which Bayesian analysis is applied to rheological micromechanical models in cement paste, self-compacting mortar, and self-compacting concrete. As a consequence of the varied characteristics of the particles in these suspensions (in terms of materials, shapes, size distributions, etc.), as well as their random nature, it seems appropriate to study these systems with probabilistic models. The Bayesian analysis, thorough Markov Chain Monte Carlo and Gibbs Sampling methods, allows the conversion of parametric-deterministic models into parametric-probabilistic models, which results in enrichment in engineering and science. The incorporation of steel fibers requires a new term in the model to account for their effect on the dynamic viscosity of SCSFRC, and this new term is also treated here with the Bayesian approach. The paper uses an extensive collection of experimental data to obtain the probability density functions of the parameters for assessing the dynamic viscosity in SCSFRC. The results obtained with these parameters' distributions are much better than those calculated with the theoretical values of the parameters, which indicates that Bayesian methods are appropriated to respond to questions in complex systems with complex models.

Calculation of Dynamic Viscosity in Concentrated Cementitious Suspensions: Probabilistic Approximation and Bayesian Analysis.

We present a new focus for the Krieger-Dougherty equation from a probabilistic point of view. This equation allows the calculation of dynamic viscosity in suspensions of various types, like cement paste and self-compacting mortar/concrete. The physical meaning of the parameters that intervene in the equation (maximum packing fraction of particles and intrinsic viscosity), together with the random nature associated with these systems, make the application of the Bayesian analysis desirable. This analysis permits the transformation of parametric-deterministic models into parametric-probabilistic models, which improves and enriches their results. The initial limitations of the Bayesian methods, due to their complexity, have been overcome by numerical methods (Markov Chain Monte Carlo and Gibbs Sampling) and the development of specific software (OpenBUGS). Here we use it to compute the probability density functions that intervene in the Krieger-Dougherty equation applied to the calculation of viscosity in several cement pastes, self-compacting mortars, and self-compacting concretes. The dynamic viscosity calculations made with the Bayesian distributions are significantly better than those made with the theoretical values.

Left ventricular phosphorylation patterns of Akt and ERK1/2 after triiodothyronine intracoronary perfusion in isolated hearts and short-term in vivo treatment in Wistar rats.

OBJECTIVES: To determine the effects of triiodothyronine (T3) intracoronary perfusion in isolated hearts and short-term administration in rats on the left ventricular (LV) phosphorylation patterns of Akt and ERK1/2. MATERIALS AND METHODS: Cardiodynamic and hemodynamic parameters were evaluated in Langendorff-perfused hearts. Left ventricles were used for histomorphometric and Western blot analyses. Short-term hyperthyroidism was established by T3 (500 µg.kg-1.d-1; subcutaneous injection) for 1 (T31d), 3 (T33d), and 10 (T310d) days. RESULTS: Isolated hearts receiving T3 perfusion did not modify LV developed pressure, +dP/dtmax, -dP/dtmin, heart rate, and coronary perfusion pressure compared with vehicle-perfused hearts. P-ERK1/2 and p-Akt levels in LV tissues after 5, 15, or 60 min of T3 or vehicle perfusion were similar. Compared with their time-matched controls, isolated hearts of T33d and T310d rats exhibited LV hypertrophy and increased absolute values of +dP/dtmax and -dP/dtmin (i.e., positive inotropic and lusitropic effects). P-ERK1/2 decreased in LV tissues of T31d and T310d but not in those of T33d rats, and p-Akt levels augmented in left ventricles of T33d and stayed unaltered in those of T31d and T310d rats. CONCLUSION: T3 intracoronary perfusion did not alter cardiodynamics and hemodynamics nor influence the activation of Akt and ERK of normal hearts. Accordingly, the rapid non-genomic effects of T3 were not evident. Short-term T3 treatment provoked cardiac hypertrophy coincidental with increased LV function and associated with transient Akt activation and cyclic ERK1/2 inhibition; which implies activation of physiological hypertrophy signaling and deactivation of pathological hypertrophy signaling, respectively.

Comparative study of acute in vitro and short-term in vivo triiodothyronine treatments on the contractile activity of isolated rat thoracic aortas.

We aimed to characterize the participation of rapid non-genomic and delayed non-genomic/genomic or genomic mechanisms in vasoactive effects to triiodothyronine (T3), emphasizing functional analysis of the involvement of these mechanisms in the genesis of nitric oxide (NO) of endothelial or muscular origin. Influences of in vitro and in vivo T3 treatments on contractile and relaxant responsiveness of isolated rat aortas were studied. in vivo T3-treatment was 500 µg·kg-1·d-1, subcutaneous injection, for 1 (T31d) and 3 (T33d) days. In experiments with endothelium- intact aortic rings contracted with phenylephrine, increasing concentrations of T3 did not alter contractility. Likewise, in vitro T3 did not modify relaxant responses induced by acetylcholine or sodium nitroprusside (SNP) nor contractile responses elicited by phenylephrine or angiotensin II in endothelium-intact aortas. Concentration- response curves (CRCs) to acetylcholine and SNP in endothelium-intact aortic rings from T31d and T33d rats were unmodified. T33d, but not T31d, treatment diminished CRCs to phenylephrine in endothelium-intact aortic rings. CRCs to phenylephrine remained significantly depressed in both endothelium-denuded and endothelium- intact, nitric oxide synthase inhibitor-treated, aortas of T33d rats. In endotheliumdenuded aortas of T33d rats, CRCs to angiotensin II, and high K+ contractures, were decreased. Thus, in vitro T3 neither modified phenylephrine-induced active tonus nor CRCs to relaxant and contractile agonists in endothelium-intact aortas, discarding rapid non-genomic actions of this hormone in smooth muscle and endothelial cells. Otherwise, T33d-treatment inhibited aortic smooth muscle capacity to contract, but not to relax, in an endothelium- and NO-independent manner. This effect may be mediated by delayed non-genomic/genomic or genomic mechanisms.

A Novel Approach to Describe the Time-Temperature Conversion among Relaxation Curves of Viscoelastic Materials.

Time and temperature, besides pressure in a lesser extent, represent the most significant variables influencing the rheological behavior of viscoelastic materials. These magnitudes are each other related through the well-known Time-Temperature Superposition (TTS) principle, which allows the master curve referred to relaxation (or creep) behavior to be derived as a material characteristic. In this work, a novel conversion law to interrelate relaxation curves at different temperatures is proposed by assuming they to be represented by statistical cumulative distribution functions of the normal or Gumbel family. The first alternative responds to physical considerations while the latter implies the fulfillment of extreme value conditions. Both distributions are used to illustrate the suitability of the model when applied to reliable derivation of the master curve of Polyvinil-Butyral (PVB) from data of experimental programs. The new approach allows not only the TTS shift factors to be estimated by a unique step, but the whole family of viscoelastic master curves to be determined for the material at any temperature. This represents a significant advance in the characterization of viscoelastic materials and, consequently, in the application of the TTS principle to practical design of viscoelastic components.

Multivariate stabilizing sexual selection and the evolution of male and female genital morphology in the red flour beetle.

Male genitals are highly divergent in animals with internal fertilization. Most studies attempting to explain this diversity have focused on testing the major hypotheses of genital evolution (the lock-and-key, pleiotropy, and sexual selection hypotheses), and quantifying the form of selection targeting male genitals has played an important role in this endeavor. However, we currently know far less about selection targeting female genitals or how male and female genitals interact during mating. Here, we use formal selection analysis to show that genital size and shape is subject to strong multivariate stabilizing sexual selection in both sexes of the red flour beetle, Tribolium castaneum. Moreover, we show significant sexual selection on the covariance between the sexes for specific aspects of genital shape suggesting that male and female genitalia also interact to determine the successful transfer of a spermatophore during mating. Our work therefore highlights the important role that both male and female genital morphologies play in determining mating success and that these effects can occur independently, as well as through their interaction. Moreover, it cautions against the overly simplistic view that the sexual selection targeting genital morphology will always be directional in form and restricted primarily to males.

Fatigue Assessment Strategy Using Bayesian Techniques.

Different empirical models have been proposed in the literature to determine the fatigue strength as a function of lifetime, according to linear, parabolic, hyperbolic, exponential, and other shaped solutions. However, most of them imply a deterministic definition of the S-N field, despite the inherent scatter exhibited by the fatigue results issuing from experimental campaigns. In this work, the Bayesian theory is presented as a suitable way not only to convert deterministic into probabilistic models, but to enhance probabilistic fatigue models with the statistical distribution of the percentile curves of failure probability interpreted as their confidence bands. After a short introduction about the application of the Bayesian methodology, its advantageous implementation on an OpenSource software named OpenBUGS is presented. As a practical example, this methodology has been applied to the statistical analysis of the Maennig fatigue S-N field data using the Weibull regression model proposed by Castillo and Canteli, which allows the confidence bands of the S-N field to be determined as a function of the already available test results. Finally, a question of general interest is discussed as that concerned to the recommendable number of tests to carry out in an experimental S-N fatigue program for achieving "reliable or confident" results to be subsequently used in component design, which, generally, is not adequately and practically addressed by researchers.

Effect of ultrasound image enhancement software on the quality of vision of regional anesthesia needles.

BACKGROUND: Our objective was to evaluate and compare the visualization of different types of needles with or without ultrasound image enhancement software, both in biological tissues and artificial models. METHODS: This is an observational study on fresh porcine tissue and gelatin models. Six types of plexus needles were studied. The same anesthesiologist performed in-plane punctures with each needle at 30°, 40° and 50° in both 2D mode and using software-based enhanced mode without changing position, generating 72 images. The images were evaluated blind by 38 anesthesiologists with at least two years of experience in ultrasound and rated from 0 to 10. A univariate and multivariate analysis was performed to identify differences between the images according to needle, mode, angle and experimental model. We described the results as mean (standard deviation). RESULTS: The Echoplex needle, 8.31 (1.94), was significantly better than the Sonoplex needle, 7.53 (2.16), P=0.0003, and both were significantly better than the other needles (P<0.0001). Significant differences were also found in favor of the gelatin model, 7.26 (2.48) vs. 6.24 (3.67), P<0.0001, and with ultrasound image enhancement software, 8.59 (1.55) vs. 4.91 (3.31), P<0.0001. These differences were confirmed by multivariate analysis. CONCLUSIONS: Although there are differences between the different types of needles used with ultrasound visualization strategies, ultrasound image enhancement software provides good visualization, regardless of the model chosen.

The Geometry of Nutrient Space-Based Life-History Trade-Offs: Sex-Specific Effects of Macronutrient Intake on the Trade-Off between Encapsulation Ability and Reproductive Effort in Decorated Crickets.

Life-history theory assumes that traits compete for limited resources, resulting in trade-offs. The most commonly manipulated resource in empirical studies is the quantity or quality of diet. Recent studies using the geometric framework for nutrition, however, suggest that trade-offs are often regulated by the intake of specific nutrients, but a formal approach to identify and quantify the strength of such trade-offs is lacking. We posit that trade-offs occur whenever life-history traits are maximized in different regions of nutrient space, as evidenced by nonoverlapping 95% confidence regions of the global maximum for each trait and large angles (θ) between linear nutritional vectors and Euclidean distances (d) between global maxima. We then examined the effects of protein and carbohydrate intake on the trade-off between reproduction and aspects of immune function in male and female Gryllodes sigillatus. Female encapsulation ability and egg production increased with the intake of both nutrients, whereas male encapsulation ability increased with protein intake but calling effort increased with carbohydrate intake. The trade-offs between traits was therefore larger in males than in females, as demonstrated by significant negative correlations between the traits in males, nonoverlapping 95% confidence regions, and larger estimates of θ and d. Under dietary choice, the sexes had similar regulated intakes, but neither optimally regulated nutrient intake for maximal trait expression. We highlight the fact that greater consideration of specific nutrient intake is needed when examining nutrient space-based trade-offs.

Effects of indomethacin on prostanoid synthesis and vasomotor responsiveness in endothelium-denuded abdominal and thoracic aortas of Wistar rats.

In endothelium-denuded abdominal (but not thoracic) aortas of rats, the nonselective cyclooxygenase (COX) inhibitor, indomethacin, suppressed contractions evoked by α-adrenergic agonists hypothetically mediated by prostanoids. We aimed to identify these non-endothelial-derived contractile prostanoids released by α-adrenergic receptors activation. Endothelium-denuded abdominal and thoracic aortas of Wistar rats were used for biochemical and functional analyses. Western blot analysis showed that COX-1 and COX-2 protein levels were respectively equivalent in endothelium-denuded abdominal and thoracic aortas. Enzyme immunoassay data supported direct evidence of phenylephrine-stimulated release of prostanoids (PGI2, PGE2, and PGF2α) by thoracic and abdominal aortas without endothelium, and their almost complete inhibition by 1 µM indomethacin. Isometric force measurements established that 10 µM indomethacin-but no lower concentrations-inhibited the contractions evoked by phenylephrine in endothelium-denuded abdominal aorta. In this preparation, 10 µM indomethacin also depressed the contractions provoked by angiotensin II and high K+ (80 mM). In fact, indomethacin (up to 1 mM) caused concentration-dependent reductions in all abovementioned contractile responses. In endothelium-denuded thoracic aortas, however, only 1 mM indomethacin significantly depressed the contractile activity stimulated by either phenylephrine, angiotensin II, or high K+. Hence, there was a clear quantitative difference in response to indomethacin between abdominal and thoracic aortas without endothelium. Altogether, the results indicate that prostanoids induced by phenylephrine in abdominal and thoracic aortas were derived from non-endothelial COX-mediated metabolism; notably, the decrease in prostanoid synthesis could not account for the inhibition of vasoconstrictor responses by indomethacin: Through COX-independent actions, indomethacin inhibited aortic smooth muscle contractility.

Distributed One-Class Support Vector Machine.

This paper presents a novel distributed one-class classification approach based on an extension of the ν-SVM method, thus permitting its application to Big Data data sets. In our method we will consider several one-class classifiers, each one determined using a given local data partition on a processor, and the goal is to find a global model. The cornerstone of this method is the novel mathematical formulation that makes the optimization problem separable whilst avoiding some data points considered as outliers in the final solution. This is particularly interesting and important because the decision region generated by the method will be unaffected by the position of the outliers and the form of the data will fit more precisely. Another interesting property is that, although built in parallel, the classifiers exchange data during learning in order to improve their individual specialization. Experimental results using different datasets demonstrate the good performance in accuracy of the decision regions of the proposed method in comparison with other well-known classifiers while saving training time due to its distributed nature.

La construcción de un nuevo campo de conocimiento: el caso de la bioética en Venezuela / A construção de um novo campo de conhecimento: o caso da bioética na Venezuela / Building a new field of knowledge: the case of bioethics in Venezuela

En este artículo se describe y analiza el proceso de institucionalización de la bioética en Venezuela, en términos tanto de su organización, composición y actividades, como del nivel de gestión pública en el cual se ha institucionalizado. El método empleado es documental, estructurado de manera cronológico-descriptiva, el cual permite establecer relaciones, diferencias, etapas, posiciones y estado actual de los conocimientos en el área de estudio. Se concluye que dicho proceso no ha estado articulado con un programa de formación de capacidades, tanto para el área de investigación como para la gestión.

In this article the process of institutionalization of bioethics in Venezuela is described and analyzed, in terms both of its organization, composition and activities and the level of public management in which it has been institutionalized. The method employed is documental, structured in a chronological-descriptive way, which allowed establishing relations, differences, stages, positions and current state of knowledge in the field of study. It was concluded that such process has not been articulated with a program for training capacities, both for research field and management.

Neste artigo se descreve e analisa o processo de institucionalização da bioética na Venezuela, em termos tanto de sua organização, composição e atividades, como do nivel de gestão pública no qual foi institucionalizada. O método empregado é documental, estruturado de maneira cronológico-descritiva, que permitiu estabelecer relações, diferenças, etapas, posições e estado atual dos conhecimentos na área de estudo. Se conclui que o dito processo não esteve articulado com um programa de formação de capacidades, tanto para a área de investigação como para a gestão.

Activation of upregulated angiotensin II type 2 receptors decreases carotid pulse pressure in rats with suprarenal abdominal aortic coarctation.

Our aim was to determine whether angiotensin type 2 receptors (AT2R) are involved in the depression of carotid pulse pressure (PP) in rats with suprarenal aortic coarctation (SrC). We tested the effects of losartan, PD123319, and CGP42112 on PP in SrC and Sham-operated anesthetized rats. PP increased in SrC rats. Neither losartan nor PD123319 affected PP in SrC and Sham-operated rats. CGP42112 reduced PP, in SrC rats, combined with losartan. Moreover, PD123319 blocked this effect. AT2R protein increased in the thoracic aortas of SrC rats. Thus, upregulated AT2R stimulation by CGP42112 mediates depression of PP in rats under pressure overloading.

A minimum volume covering approach with a set of ellipsoids.

A technique for adjusting a minimum volume set of covering ellipsoids technique is elaborated. Solutions to this problem have potential application in one-class classification and clustering problems. Its main original features are: 1) It avoids the direct evaluation of determinants by using diagonalization properties of the involved matrices, 2) it identifies and removes outliers from the estimation process, 3) it avoids binary variables resulting from the combinatorial character of the assignment problem that are replaced by continuous variables in the range [0,1], 4) the problem can be solved by a bilevel algorithm that in its first level determines the ellipsoids and in its second level reassigns the data points to ellipsoids and identifies outliers based on an algorithm that forces the Karush-Kuhn-Tucker conditions to be satisfied. Two theorems provide rigorous bases for the proposed methods. Finally, a set of examples of application in different fields is given to illustrate the power of the method and its practical performance.

Lack of heterologous receptor desensitization induced by angiotensin II type 1 receptor activation in isolated normal rat thoracic aorta.

We tested whether heterologous receptor desensitization induced by activation of AT1 receptors may explain the purported relaxation produced by angiotensin II in normal rat aorta. Also, the role for AT2 receptors in the promotion of vasodilation was studied. In endothelium-intact and endothelium-denuded aortic rings, angiotensin II elicited biphasic contractions, which were significantly depressed when repeated in each tissue. Angiotensin II produced biphasic responses on phenylephrine preconstricted endothelium-intact and endothelium-denuded tissues, without reducing precontractile tone. These responses were abolished in the presence of the AT1 receptor antagonist losartan, but no relaxing responses to angiotensin II were uncovered. PD123319 did not influence angiotensin II responses in endothelium-intact tissues precontracted with phenylephrine; thus, under AT2 receptors blockade the contractile effects of angiotensin II were not overexposed. In conclusion, angiotensin II-induced biphasic responses can be attributed to AT1 receptors activation and rapid desensitization with time. Desensitization proved to be homologous in nature, since precontractile tone induced by phenylephrine was not depressed by angiotensin II (i.e., angiotensin II did not induce heterologous α1-adrenergic receptors desensitization). We found no functional evidence of the participation of AT2 receptors in angiotensin II elicited biphasic contractions. Angiotensin II does not exert relaxant effects in normal rat aorta.

Effects induced by inhibitors of the phosphatidylinositol 3-kinase/Akt and nitric oxide synthase/guanylyl cyclase pathways on the isometric contraction in rat aorta: a comparative study.

This work was aimed to determine whether isometric contraction in Wistar rat aorta is related to the phosphatidylinositol 3-kinase (PI3K)/Akt-dependent activation of endothelial nitric oxide synthase (eNOS). Basically, we hypothesized that additional increases in active tone occur after the pharmacological inhibition of a transduction pathway involved in NO synthesis or action. In intact aortic rings contracted with phenylephrine or high K(+), the cumulative administration of the PI3K inhibitor, LY294002, elicited significant decreases--but not supplementary increases--in tone. In endothelium-intact tissues, on the other hand, the Akt1/2 kinase inhibitor did not alter phenylephrine- and K(+)-induced isometric contractions. The PI3K inhibitor wortmannin (1 × 10(-7) m) produced a significant supplementary contraction only in endothelium-intact aortic rings precontracted with phenylephrine. Higher concentrations of this inhibitor produced relaxations of phenylephrine and high K(+)-constricted endothelium-intact and endothelium-denuded aortic rings. LY294002 and wortmannin did not cause any potentiating effect on phenylephrine- and angiotensin II-induced concentration-dependent contractile responses in endothelium-intact tissues. In intact aortic rings contracted with phenylephrine or high K(+), the addition of the NOS inhibitor, L-NAME, or the guanylyl cyclase inhibitor, ODQ, further augmented tone in a concentration-dependent manner, and these supplementary contractions were significantly reduced by endothelium removal. Taken together, our data suggest that the PI3K/Akt pathway is not counteracting aortic isometric contractions by activation of the eNOS. It appears, on the other hand, that the smooth muscle PI3K can stimulate contraction without activation of the protein kinase Akt in response to GPCR agonists and high K(+).

Acute intravenous injection and short-term oral administration of N(G) -nitro-L-arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension, but not inhibition of acetylcholine-induced hypotensive responses.

In experiments in vivo, we studied whether the endothelial dysfunction induced by nitric oxide (NO) synthesis inhibition is simultaneously or sequentially manifested as a reduced level of endothelium-dependent agonist-induced vasodilatation, an increased responsiveness to vasoconstrictors, and hypertension. Vascular responses to acetylcholine, phenylephrine, and angiotensin II were measured in pithed rats after acute intravenous injection (100 mg/kg) and short-term oral administration of N(G) -nitro-L-arginine methyl ester (L-NAME; 60 mg/kg per day) for 1 and 3 days (L-NAME(1d) and L-NAME(3d), respectively). Pithed rats were chosen because drug-induced cardiovascular responses reflect only peripheral effects. Parallel experiments examined mean arterial pressure (MAP) values in anesthetized rats. After short-term L-NAME(1d) and L-NAME(3d) treatments, the MAP was significantly elevated in anesthetized but not pithed rats. Acute intravenous administration of L-NAME elevated MAP in pithed rats. Intravenous infusion of phenylephrine was used to compensate for the pressor response induced by L-NAME in pithed animals. The maximum decrease and duration of the hypotensive responses to acetylcholine were unaltered by the acute and both short-term L-NAME treatments in pithed rats. These treatments, on the other hand, increased phenylephrine- and angiotensin II-induced pressor responses in pithed animals. In isolated aortic rings prepared from pithed rats treated acutely and short-term with L-NAME, acetylcholine-induced relaxations were inhibited. Thus, the inhibition of NO-dependent vasodilator tone after acute intravenous injection and short-term oral L-NAME administration may be associated with vascular smooth muscle hyper-responsiveness to pressor agonists and hypertension, whereas the hypotensive responses to acetylcholine could not be associated with the L-NAME-induced endothelial dysfunction in pithed rats.