Selective area growth of AlN/GaN nanocolumns on (0001) and (11-22) GaN/sapphire for semi-polar and non-polar AlN pseudo-templates.

Despite the strong interest in optoelectronic devices working in the deep ultraviolet range, no suitable low cost, large-area, high-quality AlN substrates have been available up to now. The aim of this work is the selective area growth of AlN nanocolumns by plasma assisted molecular beam epitaxy on polar (0001) and semi-polar (11-22) GaN/sapphire templates. The resulting AlN nanocolumns are vertically oriented with semi-polar {1-103} top facets when grown on (0001) GaN/sapphire, or oriented at 58° from the template normal and exposing {1-100} non-polar top facets when growing on (11-22) GaN/sapphire, in both cases reaching filling factors ≥80%. In these kinds of arrays each nanostructure could function as a building block for an individual nano-device or, due to the large filling factor values, the overall array top surfaces could be seen as a quasi (semi-polar or non-polar) AlN pseudo-template.

Titanium induced polarity inversion in ordered (In,Ga)N/GaN nanocolumns.

We report on the formation of polarity inversion in ordered (In,Ga)N/GaN nanocolumns grown on a Ti-masked GaN-buffered sapphire substrate by plasma assisted molecular beam epitaxy. High-resolution transmission electron microscopy and electron energy-loss spectroscopy reveal a stacking fault-like planar defect at the homoepitaxial GaN interface due to Ti incorporation, triggering the generation of N-polar domains in Ga-polar nanocolumns. Density functional theory calculations are applied to clarify the atomic configurations of a Ti monolayer occupation on the GaN (0002) plane and to prove the inversion effect. The polarity inversion leads to an enhanced indium incorporation in the subsequent (In,Ga)N segment of the nanocolumn. This study provides a deeper understanding of the effects of Ti mask in the well-controlled selective area growth of (In,Ga)N/GaN nanocolumns.

Distinguishing cubic and hexagonal phases within InGaN/GaN microstructures using electron energy loss spectroscopy.

3D InGaN/GaN microstructures grown by metal organic vapor phase epitaxy (MOVPE) and molecular beam epitaxy (MBE) have been extensively studied using a range of electron microscopy techniques. The growth of material by MBE has led to the growth of cubic GaN material. The changes in these crystal phases has been investigated by Electron Energy Loss Spectroscopy, where the variations in the fine structure of the N K-edge shows a clear difference allowing the mapping of the phases to take place. GaN layers grown for light emitting devices sometimes have cubic inclusions in the normally hexagonal wurtzite structures, which can influence the device electronic properties. Differences in the fine structure of the N K-edge between cubic and hexagonal material in electron energy loss spectra are used to map cubic and hexagonal regions in a GaN/InGaN microcolumnar device. The method of mapping is explained, and the factors limiting spatial resolution are discussed.

Light-emitting-diodes based on ordered InGaN nanocolumns emitting in the blue, green and yellow spectral range.

The growth of ordered arrays of InGaN/GaN nanocolumnar light emitting diodes by molecular beam epitaxy, emitting in the blue (441 nm), green (502 nm), and yellow (568 nm) spectral range is reported. The device active region, consisting of a nanocolumnar InGaN section of nominally constant composition and 250 to 500 nm length, is free of extended defects, which is in strong contrast to InGaN (planar) layers of similar composition and thickness. Electroluminescence spectra show a very small blue shift with increasing current (almost negligible in the yellow device) and line widths slightly broader than those of state-of-the-art InGaN quantum wells.

Selective area growth of In(Ga)N/GaN nanocolumns by molecular beam epitaxy on GaN-buffered Si(111): from ultraviolet to infrared emission.

Selective area growth of In(Ga)N/GaN nanocolumns was performed on GaN-buffered Si(111) substrates by plasma-assisted molecular beam epitaxy. Undoped and Si-doped GaN buffer layers were first grown on Si(111) substrates, showing photoluminescence excitonic emission without traces of other low energy contributions, in particular, the yellow band. The GaN buffer surface roughness (between 10 and 14 nm, the rms value in a 10 × 10 µm(2) area) was low enough to allow the fabrication of a thin (7 nm thick) well defined Ti nanohole mask, for the selective area growth. Ordered In(Ga)N/GaN nanocolumns emitting from the ultraviolet (3.2 eV) to the infrared (0.78 eV) were obtained. The morphology and the emission efficiency of the In(Ga)N/GaN nanocolumns emitting at a given wavelength could be substantially improved by tuning the In/Ga and total III/N ratios. An estimated internal quantum efficiency of 36% was derived from photoluminescence data for green emitting nanocolumns.

Plasmon excitation in electron energy-loss spectroscopy for determination of indium concentration in (In,Ga)N/GaN nanowires.

We demonstrate the potential of low-loss electron energy-loss spectroscopy in transmission electron microscopy as a quick and straightforward method to determine the local indium compositions in (In,Ga)N/GaN nanowires. The (In,Ga)N/GaN nanowire heterostructures are grown by plasma assisted molecular beam epitaxy on Si(111) substrates in a self-assembled way, and on patterned GaN templates in an ordered way. A wide range of indium contents is realized by varying the substrate temperatures. The plasmon peak in low-loss electron energy-loss spectroscopy exhibits a linear relation with respect to indium concentration in (In,Ga)N nanowires, allowing for a direct compositional analysis. The high spatial resolution of this method in combination with structural information from transmission electron microscopy will contribute to a basic understanding of the lattice pulling effect during (In,Ga)N/GaN nanowire growth.

Características del hábito tabáquico y tratamiento en fumadores de edad avanzada / Characteristics of smoking in adult smokers

Objetivo: Analizar las características del hábito de fumar enlos pacientes con edad mayor o igual de 60 años atendidosen una consulta de tabaquismo y valorar sus diferencias conrespecto al resto de los pacientes de menor edad.Población y métodos: Se valoraron 62 pacientes mayoresde 59 años vistos en la consulta de tabaquismo de nuestrohospital. Se analizó el sexo, edad, número de cigarrillosconsumidos al día, intentos previos de abandono, mediciónde monóxido de carbono, test de Fagerström, test de Richmond,motivación para dejar de fumar y tratamiento. Estasvariables se compararon con los 384 pacientes menores de60 años que se atendieron en la consulta en el mismo periodode tiempo.Resultados: Se incluyeron 446 pacientes con una edad mediaglobal de 46,57 años (SD 10,7) de los cuales 243 eranhombres (54,5%) y 203 mujeres (45,5%). De los pacientesincluidos, 62 tenían una edad igual o mayor de 60 años, loque representa un 13,45% del total. Se encontraron diferenciassigni cativas en el porcentaje de pacientes que fumabanmenos de 10 cigarrillos al día con una p = 0.006, un 5% enlos < 60 años con un IC 95% del 3% al 7%, mientras queen los mayores de 59 años era del 16,4% con un IC 95%de 7,4% a 25,4%. También se encontraron diferencias en lamedición del CO, siendo más elevada en el grupo de menoresde 60 años. La media de CO en menores de 60 años erade 18,48 con un IC del 95% de 17,5 a 19,46. En los mayoresde 59 años era de 14,69 con un IC del 95% de 12,77 a 16,61(p=0.012). En cuanto a los motivos para querer dejar defumar, en el grupo de mayores el 50% referían padecer síntomasrelacionados con el consumo de tabaco y el 38,7% lohacían por temor a sufrir enfermedades en el futuro. En elgrupo de menores de 60 años, el 40, 6% el motivo era sufrirsíntomas relacionados con el tabaco y el 43% por preservarsu salud futura. Más del 50% de los pacientes mayores tuvocomo tratamiento algún sustitutivo de nicotina (AU)

Objective: To analise the smoking characteristics ofsmokers over 60 years old who attend to a smokers´clinicand to study the differences with younger smokers.Subjects and methods: We studied 62 smokers over59 years old who atended the smokers´clinic. We studied gender, age, number of cigarettes smoked daily, previousattempt to quit, measurement of CO in expired air, FTNquestionnaire, Richmond Questionnaire, motivation to quitand treatmen. These topics were compared with 384 youngersmokers who atended the clinic during the same periodof time.Results: 446 smokers were included, mean age 46,57 (SD10,7), 243 were male (54,5%) and 203 women (45,5%). 62smokers were 60 or more years old (13,45%). 5% (95% IC3%-7%) of smokers less than 60 years old smoked less than10 cigarettes per day, while 16,4% (IC 95% 12,77%-16,61%)of those over 60 years, p = 0.006. Measuremnt of CO was18,48 (95% IC 17,5- 19,46) in those less than 60 years oldwhile it was 14,69 (IC 95% 12,77 - 16,61) in those over 60years old. (p=0.012). Smokers over 60 years old referedsymptoms related to smoking as the most imprtant motivationto quit (50%) and 38,7 % expressed fear to developsmoking related disorders in the near future. Smokers lessthan 60 years old expressed fear to develop diseases in thefuture as the most important motivation to quit (43%) andsymptoms related to smoking in 40%. More than 50% ofsmokers over 60 years old were treated with nicotine replacementtherapy. (NRT)Conclusion: Smokers over 60 years old ask for help to quitdue to symptoms related to smoking. The main motivation to quit in smokers less than 60 years old is fear to developsmoking related disorders. Smokers over 60 years old smokeless than the younger ones. NRT is used more frequentely insmokers over 60 years old (AU)

Resultados de una consulta específica para cáncer broncogénico / Results of a specific consultation for bronchogenic cancer

Introducción: El cáncer broncogénico es la primera causa de mortalidad en varones en el mundo occidental. Para un tratamiento eficaz es necesario un diagnóstico precoz del tumor.Objetivo: Evaluación de la puesta en marcha de una consulta de diagnóstico rápido para el cáncer broncogénico.Material y Métodos: Revisión de 205 pacientes diagnosticados en una consulta específica para esta patología entre septiembre 2002 y marzo del 2005.Resultados: De todos los pacientes vistos en la consulta se confirmó la sospecha de cáncer en 115 (56,1%). La mediana del tiempo diagnóstico fue de 14 días. El predominio fue de cáncer epidermoide en número absoluto, aunque por sexos en mujeres predominaba el adenocarcinoma. En 83 (72%) pacientes se llegó al diagnóstico por broncoscopia, en 24 (20,8%)por PAAF, en 3 (2,61%) por punción de adenopatía, en 1 (0,87%) por biopsia pleural y en 4 (3,48%) por cirugía diagnóstica.Discusión: La prioridad en esta patología es el diagnóstico precoz hasta que dispongamos de un método de screening eficaz. En nuestra área, hemos implantado una consulta específica para esta patología que evita ingresos innecesarios y acelera el diagnóstico en lo posible. Los datos epidemiológicos obtenidos son similares a otras series. En el momento deldiagnóstico, 61 (64,21%) pacientes tenían un estadio IIIA o superior. La necesidad de derivar a estos pacientes a otros centros para tratamiento dificulta un abordaje integral de esta patología

Introduction: Bronchogenic cancer is the first cause of mortality in men in the Western world. An early diagnosis of the tumor is necessary for effective treatment.Objective: Evaluation of the initiation of a rapid diagnostic consultation for bronchogenic cancer.Material and methods: Review of 205 patients diagnosed in a specific consultation for this disease between September 2002 and March 2005.Results: Suspicion of cancer in all the patients seen in the consultation was confirmed in 115 (56.1%). Median diagnostic time was 14 days. The predominance was squamous cell carcinoma in absolute number, although adenocarcinoma predominated in women by gender. Diagnosis was reached in 83 (72%) of the patients by bronchoscopy, in 24 (20.8%) by FNAB, in 3 (2.61%) by adenopathy puncture, in 1 (0.87%) by pleural biopsy and in 4 (3.48%) by diagnostic surgery.Discussion: Priority in this disease is the early diagnosis until we have an effective screening method. In our area, we have established a specific consultation for this disease that avoids unnecessary admissions and accelerates the diagnosis as much as possible. The epidemiological data obtained are similar to other series. At the time of the diagnosis, 61 (64.21%)of the patient had stage IIIA or greater. The need to refer these patients to other centers for treatment makes an complete approach of this disease difficult (AU)

Diastereoselective tandem 6-exo carbolithiation intramolecular ring opening in (-)-8-aminomenthol-derived perhydrobenzoxazines. A new synthesis of enantiopure 4-substituted tetrahydro isoquinolines and 2-azabenzonorbornanes.

Aryllithiums prepared by bromine-lithium interchange in chiral 2-(o-bromophenyl)-substituted perhydro-1,3-benzoxazines participate in the intramolecular 6-exo carbolithiation reaction with unactivated double bonds attached to the nitrogen substituent of the heterocycle. When the reaction time is extended or no TMEDA is used, the cyclized lithium intermediates react intramolecularly with the N,O-acetal system leading to 2-azabenzonorbornane derivatives. The reactions are highly stereoselective and constitute a high-yielding synthesis of enantiopure 4-substituted tetrahydroisoquinolines or 7-substituted 2-azabenzonorbornanes.

Different sensitivity of isoprenaline-induced responses in ventricular muscle to sodium nitroprusside in normotensive and spontaneously hypertensive rats.

1. The aim of the present work was to study the possible modulatory role of nitric oxide (NO) on the positive inotropic effect induced by the beta-adrenoceptor agonist isoprenaline in myocardial contractility, and whether this modulation is altered by hypertension. 2. The study was performed using right ventricular strips from the hearts of 6-month-old male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The contractile force of electrically-stimulated ventricular strips was measured by a force-displacement transducer. 3. Isoprenaline (from 10 nmol l(-1) to 10 micromol l(-1)) induced a concentration-dependent increase in cardiac contractility in strips from both rat strains. This positive inotropic effect to isoprenaline was reduced by the NO donor sodium nitroprusside (SNP, 0.1 mmol l(-1)) in muscles from WKY rats and slightly increased in those from SHR. The SNP-induced increase in strips from SHR was abolished by superoxide dismutase (100 U ml(-1)). 4. N(G)-nitro-arginine-methyl ester (L-NAME, 0.1 mmol l(-1)) and 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10 micromol l(-1)), respective inhibitors of NO synthase and guanylate cyclase, increased the response to isoprenaline in muscles from WKY rats, whereas it was unaltered in strips from SHR. 5. In strips from WKY rats, the combination of ODQ and SNP produced an increase in the response elicited by isoprenaline, which was similar to that observed with ODQ or L-NAME. 8-Br-cyclicGMP (8-Br-cGMP, 0.1 mmol l(-1)), a permeable and structural cGMP analogue, decreased the effect induced by isoprenaline only in muscles from WKY rats. 6. These results suggest that the positive inotropic response to isoprenaline in ventricular strips from WKY rats is negatively modulated by NO, and positively by superoxide anions in those from SHR. The lack of a modulatory response to NO in ventricular strips from SHR is probably a result of an alteration of mechanisms in NO-signalling pathway downstream of cGMP formation in SHR hearts.

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats.

The aim of the present study was to assess the alterations in cardiac Ca2+ homeostasis induced by hypertension using electrically paced right ventricular strips from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2 Basal contractile force was higher in SHR than in WKY. Similarly, the beta-adrenoceptor agonist isoprenaline (10 nM-10 microM) induced a concentration-dependent positive inotropic effect that was higher in SHR than in WKY, which was in turn inhibited by the beta-adrenoceptor antagonist propranolol (1 microM) in both strains. 3 Preincubation of strips with the L-type Ca2+ channel blockers, nifedipine (1 microM) or verapamil (10 microM), markedly inhibited the isoprenaline response, the inhibition being higher in SHR than in WKY. However, this inhibition was minor by the T-type Ca2+ channel blocker mibefradil (10 microM). 4 Bay K 8644 (10 nM-10 microM), a L-type Ca2+ channel activator induced a concentration-dependent positive inotropic effect, that was greater in SHR than WKY. 5 Nifedipine and verapamil (both 0.1 nM-10 microM) inhibited in a concentration-dependent way the inotropic effect induced by 0.3 microM isoprenaline or 1 microM Bay K 8644. The inhibition was higher in SHR than in WKY. Mibefradil (0.1 nM-10 microM) only clearly inhibited the isoprenaline and Bay K 8644 inotropic effects at 10 microM in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 nM-10 microM), was a more effective depressor of isoprenaline-induced response in SHR than in WKY. 7 These results suggest that cardiac Ca2+ homeostasis in SHR ventricular strips is altered compared with those of WKY, showing an increased Ca2+ entry through L-type Ca2+ channels and release from sarcoplasmic reticulum; the participation of T-type Ca2+ channels are irrelevant in this tissue.

Role of K+ channels and sodium pump in the vasodilation induced by acetylcholine, nitric oxide, and cyclic GMP in the rabbit aorta.

The endothelium-dependent relaxation caused by acetylcholine (ACh) in rabbit aorta segments was reduced by the nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester and by blockade of: Na+ pump with ouabain, large-conductance Ca2+-activated K+ (BK(Ca)) channels with charybdotoxin (ChTx), or voltage-dependent K+ (Kv) channels with 4-aminopyridine (4-AP). ACh relaxation was unaltered by glibenclamide, apamin, and Ba2+, blockers of ATP-sensitive K+ channels, small-conductance Ca2+-activated K+ channels, and inward rectifier K+ channels, respectively. The relaxation induced by exogenous NO and 8-bromocyclic GMP (8-BrcGMP) was similar in intact and endothelium-denuded segments, and it was reduced or unaltered by the same drugs used in the case of ACh. However, a 4-AP concentration 20-fold higher was necessary to reduce exogenous NO relaxation. These data suggest a resemblance in the mechanisms implicated in the relaxation elicited by ACh, exogenous NO, and 8-BrcGMP. Therefore, the relaxation caused by ACh is mainly mediated by endothelial NO, which in turn, enhances cGMP levels; this messenger appears to be the major one responsible for the smooth muscle cell hyperpolarization in the relaxation elicited by ACh, which is mediated by activation of the Na+ pump and ChTx- and 4-AP-sensitive K+ channels, likely BK(Ca) and Kv channels.

Mechanisms involved in the cellular calcium homeostasis in vascular smooth muscle: calcium pumps.

The regulation of cytosolic Ca2+ homeostasis is essential for cells, and particularly for vascular smooth muscle cells. In this regulation, there is a participation of different factors and mechanisms situated at different levels in the cell, among them Ca2+ pumps play an important role. Thus, Ca2+ pump, to extrude Ca2+; Na+/Ca2+ exchanger; and different Ca2+ channels for Ca2+ entry are placed in the plasma membrane. In addition, the inner and outer surfaces of the plasmalemma possess the ability to bind Ca2+ that can be released by different agonists. The sarcoplasmic reticulum has an active role in this Ca2+ regulation; its membrane has a Ca2+ pump that facilitates luminal Ca2+ accumulation, thus reducing the cytosolic free Ca2+ concentration. This pump can be inhibited by different agents. Physiologically, its activity is regulated by the protein phospholamban; thus, when it is in its unphosphorylated state such a Ca2+ pump is inhibited. The sarcoplasmic reticulum membrane also possesses receptors for 1,4,5-inositol trisphosphate and ryanodine, which upon activation facilitates Ca2+ release from this store. The sarcoplasmic reticulum and the plasmalemma form the superficial buffer barrier that is considered as an effective barrier for Ca2+ influx. The cytosol possesses different proteins and several inorganic compounds with a Ca2+ buffering capacity. The hypothesis of capacitative Ca2+ entry into smooth muscle across the plasma membrane after intracellular store depletion and its mechanisms of inhibition and activation is also commented.

The cardiac acetylcholine-activated, inwardly rectifying K+-channel subunit GIRK1 gives rise to an inward current induced by free oxygen radicals.

Reactive oxygen species (ROS) play a crucial role in pathophysiology of the cardiovascular system. The present study was designed to analyze the redox sensitivity of G-protein-activated inward rectifier K+ (GIRK) channels, which control cardiac contractility and excitability. GIRK1 subunits were heterologously expressed in Xenopus laevis oocytes and the resulting K+ currents were measured with the two-electrode voltage clamp technique. Oxygen free radicals generated by the hypoxanthine/xanthine oxidase system led to a marked increase in the current through GIRK channels, termed superoxide-induced current (I(SO)). Furthermore, I(SO) did not depend on G-protein-dependent activation of GIRK currents by coexpressed muscarinic m2-receptors, but could also be observed when no agonist was present in the bathing solution. Niflumic acid at a concentration of 0.5 mmol/l did not abolish I(SO), whereas 100 micromol/l Ba2+ attenuated I(SO) completely. Catalase (10(6) i.u./l) failed to suppress I(SO), whereas H2O2 concentration was kept close to zero, as measured by chemiluminescence. Hence, we conclude that O2*- or a closely related species is responsible for I(SO) induction. Our results demonstrate a significant redox sensitivity of GIRK1 channels and suggest redox-activation of G-protein-activated inward rectifier K+ channels as a key mechanism in oxidative stress-associated cardiac dysfunction.

Involvement of protein kinase C in the supersensitivity to 5-HT caused by oxidized low-density lipoproteins.

The effect of native (n-LDL) and oxidized (ox-LDL) low-density lipoproteins and lysophosphatidylcholines (LPCs) on: (1) vasodilator responses induced by acetylcholine (ACh) in intact rabbit aorta segments, and (2) vasoconstrictor responses to serotonin (5-HT), and potassium (K+) in endothelium denuded segments was investigated. In intact vessels, 100 microg/ml ox-LDL did not modify ACh-induced relaxation, while it was diminished by 300 microg/ml ox-LDL and abolished by 50 microM LPCs. In contrast, this relaxation was unaltered by n-LDL (100 or 300 microg/ml). In deendothelialized arteries, 100 and 300 microg/ml n-LDL as well as 50 microM LPCs did not modify the contractions induced by 5-HT or K+, while 100 or 300 microg/ml ox-LDL increased the 5-HT-induced contraction, without altering those induced by 75 mM K+. Incubation with 100 or 300 microg/ml ox-LDL increased the contractile response to the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDB) (0.1-1 microM) in a concentration-dependent manner, which was blocked by staurosporine (0.1 microM), and unaltered by (50 microM) calphostin C or (50 microM) chelerythrine, the three are PKC inhibitors. Preincubation with 0.05 microM PDB increased the contraction elicited by 5-HT, while staurosporine decreased the PDB-induced contraction, and prevented the 5-HT response increase caused by 300 microg/ml ox-LDL. These results suggest that only ox-LDL reduces endothelium-dependent relaxation and elicits PKC activation, and that this activation mediates, at least in part, the vasoconstrictor response to 5-HT.

Inhibition of a store-operated Ca2+ entry pathway in human endothelial cells by the isoquinoline derivative LOE 908.

1. The novel cation channel blocker, LOE 908, was tested for its effects on Ca2+ entry and membrane currents activated by depletion of intracellular Ca2+ stores in human endothelial cells. 2. LOE 908 inhibited store-operated Ca2+ entry induced by direct depletion of Ca2+ stores with 100 nM thapsigargin or 100 nM ionomycin with an EC50 of 2 microM and 4 microM, respectively. 3. LOE 908 did not affect thapsigargin- or ionomycin-induced Ca2+ release from intracellular stores up to concentrations of 3 microM. 4. LOE 908 reversibly suppressed thapsigargin- as well as ionomycin-induced whole-cell membrane currents. 5. The LOE 908-sensitive membrane conductance corresponded to a cation permeability of 5.5 and 6.9 fold selectivity for Ca2+ over K+ in the presence of thapsigargin and ionomycin, respectively. 6. Our results suggest that the isoquinoline, LOE 908 is a novel, potent inhibitor of the store-operated (capacitive) Ca2+ entry pathway in endothelial cells.

Effect of clenbuterol on the modulation of noradrenaline release in the rat tail artery.

1. Exposure of rat tail arteries to clenbuterol, a beta 2-adrenoceptor agonist, for 20 or 90 min, did not change or increase, respectively, tritium overflow induced by electrical field stimulation in arteries preincubated with [3H]-noradrenaline (NA). This facilitatory effect was antagonized by propranolol. 2. Phentolamine increased the evoked overflow four-fold, which was not modified by 90 min incubation with clenbuterol. In rats pretreated with clenbuterol for 2 weeks, the stimulated overflow was not enhanced by this beta 2-agonist, and the increase produced by phentolamine was markedly diminished. 3. Contractile responses induced by electrical field stimulation were not modified or increased (only at low frequencies) by preincubation with clenbuterol for 20 or 90 min, respectively. This effect was inhibited by propranolol. 4. In arteries precontracted with 5-hydroxytryptamine, clenbuterol (10 nM-10 microM) produced small relaxations, which were reduced by propranolol plus phentolamine and not modified by phentolamine or 90 min exposure to clenbuterol. 5. These results indicate that prolonged exposure of rat tail arteries to clenbuterol produces a facilitation of NA release mediated by activation of presynaptic beta 2-adrenoceptors, which may be involved on the enhancement of contractile responses to electrical stimulation induced by clenbuterol. However, chronic treatment with this beta-agonist desensitizes these receptors.

Heterogeneity of endothelium-dependent mechanisms in different rabbit arteries.

The possible endothelial factors involved in endothelium-dependent relaxations induced by acetylcholine (ACh) in aorta, mesenteric and femoral arteries of rabbit were analyzed. In thoracic aorta precontracted with noradrenaline, NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB), inhibitors of nitric oxide (NO) synthase and guanylate cyclase, practically abolished ACh relaxation. This relaxation was reduced by the Na+ pump inhibition with ouabain and K(+)-free solution, and by the blockade of Ca(2+)-dependent K+ channels with tetraethylammonium (TEA). Ouabain reduced the relaxation produced by the NO donor, sodium nitroprusside (SNP). In the mesenteric artery, L-NAME and MB produced a small reduction of ACh relaxation. However, ouabain, K(+)-free medium and TEA markedly decreased this relaxation. SNP induced a relaxation which was diminished by ouabain. In segments precontracted with high K+, ACh relaxation was abolished by L-NAME and MB. In femoral arteries, L-NAME and MB reduced ACh relaxation. The stimulated cGMP concentrations caused by ACh or SNP were less in the aorta than in mesenteric and femoral arteries. These results suggest that ACh relaxation is mediated: in aorta by endothelial NO which may hyperpolarize to some extent the smooth muscle cells through the sodium pump activation, in mesenteric artery by endothelium-derived hyperpolarizing factor and NO, the latter being clearly expressed in segments contracted with high K+, and in femoral artery essentially by endothelial NO release.

Angiotensin modulation of vascular tone and adrenergic neurotransmission in cat femoral arteries.

1. AI and AII induced contractions in cat femoral arteries, which were inhibited by saralasin. 2. The response to AI was reduced by captopril and endothelium removal and by chymostatin in endothelium-denuded segments. 3. AII contractions were increased by indomethacin, L-NAME and endothelium removal. 4. AII and AI facilitated the adrenergic neurotransmission. This facilitation was inhibited by saralasin and/or captopril. 5. These data suggest: (1) AI is converted into AII in the endothelial and adventitial layer; (2) the contractions caused by AI and AII are mediated by AII receptors and are modulated by endothelial release of NO and PGI2; and (3) the existence of presynaptic AII receptors mediating the facilitation of neurotransmission caused by AI and AII.