Treatment of the cardiovascular remodeling in hypertensive patients

El corazón del hipertenso se adapta al aumento de sobrecarga que la elevación de las resistencias vasculares sistémicas conlleva aumentando del grosor de la pared ventricular. Los miocitos cardíacos adultos no proliferan, por lo que la hipertrofia cardíaca conlleva un aumento del volumen de las células musculares. Además, aparece hipertrofia e hiperplasia de los componentes non-miocitarios cardíacos. El resultado es una fibrosis perivascular e intersticial que dísminuye la dístensibilidad ventricular y ocluye los vasos coronarios, dísminuye la reserva coronaria y facilita la isquemia miocárdíca. La estructura vascular también se modifica en respuesta al aumento del estrés de la pared arterial, aumentando el cociente pared/luz vascular consecuencia de un aumento del grosor de la pared vascular o del remodelado de los componentes celulares y no celulares de la misma. Estos cambios aumentan la reactividad vascular y potencien el aumento de las resistencias vasculares periféricas caracteristico del hipertenso. La pobre correlación existente entre reducción de la presión arterial y la magnitud del remodelado cardíovascular confirma el importante papel de factores no-hemodínámicos en su patogenia (estimulación de los receptores ATI y al- adrenérgicos, edad, sexo, raza, factores genéticos, etc.). Estudíos experimentales y clínicos han demostrado que todos los antihipertensivos previenen o revierten la hipertrofia cardíaca. Sin embargo, no sólo existen díferencias entre los dístintas familias de fármacos, sino también entre los miembros de cada una de ellas. Los fármacos que inhiben el tono simpático y el sistema renina-angiotensina-aldosterona o reducen la [Ca]i son lo que mayor regresión producen, aunque el efecto parece ser más marcado con los inhibidores de la enzima de conversión. La activación refleja neurohumoral reducida por diuréticos o vasodilatadores arteriales podria explicar su incapacidad para revertir el remodelado cardiovascular a pesar de que normalizan la presión arterial. Es lógico, por tanto, sugerir que el futuro desarrollo de fármacos antihipertensivos debe ir dirigido no sólo a obtener fármacos capaces de revertir el proceso de remodelado cardíovascular del hipertenso, es decir, conseguir restaurar la estructura y función de los órganos díana. Sólo de esta forma podremos reducir la morbiortalidad del hipertenso.The heart adapts to increasing afterload, such as that which occurs in arterial hypertension with an increase in wall thickness (left ventricular hipertrophy) in order to bring wall stress back to normal. Adult cardiac myocytes are unable to proliferate, so that myocyte hypertrophy is the hallmark of left ventricular hipertrophy. Cardiac remodelling, however, involves not only myocyte growth but also hypertrophy/hyperplasia of nonmyocyte cells within the myocardium. The result is a perivascular and intersticial fibrosis that impair myocardial stiffuess. In response to increased arterial pressure, the vessel structure is altered such that the ratio of the width of the wall to the width of the lumen is increased by either an increase in mass or rearrangements of vascular smooth muscle cells and other cellular and noncellular elements of the vascular wall. These changes increased vascular reactivity, potentiated the increase in peripheral vascular resistance characteristic of hypertension and attenuated the coronary reserve to ischemic provocation. The poor correlation between blood pressure and the magnitude of cardiovascular remodelling strongly suggests a role for nonhemodynarnic factors in its pathogenesis (i.e. neurohumoral activation, neurogenic stimuli, genetic predisposition, gender, age and race). An increase in sympathetic (cd-adrenoceptors) and renin-angiotensin-aldosterone systerns (ATl receptors) piay an important role in both cardiac myocyte and nonmyocyte growth and remodelling. Experimental and clinical studies have demonstrated that all antihypertensive agents may prevent or cause regression of cardiovascular remodelling. However, despite their equipotent blood-lowering effects, there are not only marked differences in the ability of different types of antihypertensive drugs to prevent or reverse cardiovascular remodelling but also whithin the same class of pharmacological drugs. Antihypertensive drugs that modulate the sympathetic or renin-angiotensin-aldosterone systems or the intracellular free Ca concentration can reverse cardiovascular remodelling, this effect being more pronounced with ACE inhibitors. Reflex neurohumoral activation may be responsible for the failure of sorne antihypertensive drugs to produce regress cardiovascular remodelling (diuretics, vasodilators, ~-blockers with intrinsic sympathomirnetic activity and dihydropyridines), even through they reduce arterial blood presure to normotensive levels. It is therefore, logical to suggest that a more ambitious approach to modem treatrnent of hypertension would not only be to reduce elevated blood pressure, but also to introduce an important additional goal, namely to attain regression of structurally remodelled heart and vasculture to, or toward, normal structure and function. Only this therapeutic approach might truly reduce the risk of cardiovascular complications in the hipertensive patient

Mise au point d'une méthode d'extraction des lipides solubles totaux, des glucides solubles totaux et des composés phénoliques solubles totaux des organes de la vigne

Il est possible d'obtenir très rapidement et à partir d'une même poudre la totalité des lipides solubles, des glucides solubles et des composés phénoliques solubles. Le nombre d'opération nécessaires dépend des organes et a été déterminé pour les rameaux principaux, les feuilles, les rafles, les baies et les pépins.Adjustment of a method of extraction of total soluble lipids, total soluble carbohydrates and total soluble phenolic compounds from the organs of the vineIt is possible to obtain very quickly from the same powdered plant material total amounts of soluble lipids, soluble carbohydrates and soluble phenolic compounds. The number of operations required depends upon the organ concerned and has been determined for the fruiting shoots, the leaves, the rachises, the berries and the seeds

Electroreflectance spectroscopy in self-assembled quantum dots: lens symmetry

Modulated electroreflectance spectroscopy $\Delta R/R$ of semiconductor self-assembled quantum dots is investigated. The structure is modeled as dots with lens shape geometry and circular cross section. A microscopic description of the electroreflectance spectrum and optical response in terms of an external electric field (${\bf F}$) and lens geometry have been considered. The field and lens symmetry dependence of all experimental parameters involved in the $\Delta R/R$ spectrum have been considered. Using the effective mass formalism the energies and the electronic states as a function of ${\bf F}$ and dot parameters are calculated. Also, in the framework of the strongly confined regime general expressions for the excitonic binding energies are reported. Optical selection rules are derived in the cases of the light wave vector perpendicular and parallel to $$. Detailed calculation of the Seraphin coefficients and electroreflectance spectrum are performed for the InAs and CdSe nanostructures. Calculations show good agreement with measurements recently performed on CdSe/ZnSe when statistical distribution on size is considered, explaining the main observed characteristic in the electroreflectance spectra

Processing and characterisation of II-VI ZnCdMgSe thin film gain structures

Lattice-matched II-VI selenide quantum well (QW) structures grown on InP substrates can be designed for emission throughout the visible spectrum. InP has, however, strong visible-light absorption, so that a method for epitaxial lift-off and transfer to transparent substrates is desirable for vertically-integrated devices. We have designed and grown, via molecular beam epitaxy, ZnCdSe/ZnCdMgSe multi-QW gain regions for vertical emission, with the QWs positioned for resonant periodic gain. The release of the 2.7 μm-thick ZnCdSe/ZnCdMgSe multi-QW film is achieved via selective wet etching of the substrate and buffer layers leaving only the epitaxial layers, which are subsequently transferred to transparent substrates, including glass and thermally-conductive diamond. Post-transfer properties are investigated, with power and temperature-dependent surface and edge-emitting photoluminescence measurements demonstrating no observable strain relaxation effects or significant shift in comparison to unprocessed samples. The temperature dependant quantum well emission shift is found experimentally to be 0.13 nm/K. Samples capillary-bonded epitaxial-side to glass exhibited a 6 nm redshift under optical pumping of up to 35 mW at 405 nm, corresponding to a 46 K temperature increase in the pumped region; whereas those bonded to diamond exhibited no shift in quantum well emission, and thus efficient transfer of the heat from the pumped region. Atomic force microscopy analysis of the etched surface reveals a root-mean-square roughness of 3.6 nm. High quality optical interfaces are required to establish a good thermal and optical contact for high power optically pumped laser applications

Effects of peroxisome proliferator-activated receptor- activation in endothelin-dependent hypertension

Aims We analysed the chronic effects of the peroxisome proliferator-activated receptor β/δ (PPAR-β) agonist GW0742 on the renin-independent hypertension induced by deoxycorticosterone acetate (DOCA)-salt. Methods and results Rats were treated for 5 weeks with: control-vehicle, control-GW0742 (5 or 20 mg kg−1 day−1), DOCA-vehicle, DOCA-GW0742 (5 or 20 mg kg−1 day−1), DOCA-GSK0660 (1 mg kg−1 day−1), and DOCA-GSK0660-GW0742. Rats receiving DOCA-vehicle showed increased systolic blood pressure, left ventricular and kidney weight indices, endothelin-1 (ET-1), and malondialdehyde plasma levels, urinary iso-PGF2α excretion, impaired endothelium-dependent relaxation to acetylcholine, and contraction to ET-1 when compared with controls. Aortic reactive oxygen species content, NADPH oxidase activity, and p47phox, p22phox, NOX-4, glutathione peroxidase 1, hemeoxygenase-1, and preproET-1 expression were increased, whereas catalase and regulators of G protein-coupled signalling proteins (RGS)5 expression were decreased in the DOCA-vehicle group. GW0742 prevented the development of hypertension in a dose-dependent manner but the reduction of renal and cardiac hypertrophy, systemic and vascular oxidative stress markers, and improvement of endothelial dysfunction were only observed after the higher dose. GW0742, at 20 mg kg−1 day−1, attenuated ET-1 contraction by increasing RGS5 expression and restored the intracellular redox balance by reducing NADPH-oxidase activity, and by increasing the antioxidant genes expression. The PPAR-β antagonist GSK0660 prevented all vascular changes induced by GW0742 but not its antihypertensive effects. Conclusion Vascular protective effects of GW0742 operate via PPAR-β by interference with the ET-1 signalling as a result of increased expression of RGS5 and up-regulation of antioxidant genes and via PPAR-β-independent mechanisms to decrease blood pressure