Hypoxic release of calcium from the sarcoplasmic reticulum of pulmonary artery smooth muscle

The hypoxic constriction of isolated pulmonary vessels is composed of an initial transient phase (phase 1) followed by a slowly developing increase in tone (phase 2). We investigated the roles of the endothelium and of intracellular Ca2+ stores in both preconstricted and unpreconstricted intrapulmonary rabbit arteries when challenged with hypoxia (PO2 16-21 Torr). Removing the endothelium did not affect phase 1, but phase 2 appeared as a steady plateau. Removing extracellular Ca2+ had essentially the same effect as removing the endothelium. Depletion of sarcoplasmic reticulum Ca2+ stores with caffeine and ryanodine abolished the hypoxic response. Omitting preconstriction reduced the amplitude of the hypoxic response but did not qualitatively affect any of the above responses. We conclude that hypoxia releases intracellular Ca2+ from ryanodine-sensitive stores by a mechanism intrinsic to pulmonary vascular smooth muscle without the need for Ca2+ influx across the plasmalemma or an endothelial factor. Our results also suggest that extracellular Ca2+ is required for the release of an endothelium-derived vasoconstrictor.</p

Methods and related compositions for treating or preventing obesity, insulin resistance disorders, and mitochondrial-associated disorders

Provided herein are methods and compositions for treating or preventing metabolic disorders, such as obesity and diabetes. Methods may comprise modulating the activity or level of a sirtuin, such as SIRT1 or Sir2. Exemplary methods comprise contacting a cell with a sirtuin activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin, or an inhibitory compound, such as nicotinamid

Adp-ribosyl cyclase and cyclic ADP-ribose hydrolase act as a redox sensor. a primary role for cyclic ADP-ribose in hypoxic pulmonary vasoconstriction.

Hypoxic pulmonary vasoconstriction is unique to pulmonary arteries and serves to match lung perfusion to ventilation. However, in disease states this process can promote hypoxic pulmonary hypertension. Hypoxic pulmonary vasoconstriction is associated with increased NADH levels in pulmonary artery smooth muscle and with intracellular Ca(2+) release from ryanodine-sensitive stores. Because cyclic ADP-ribose (cADPR) regulates ryanodine receptors and is synthesized from beta-NAD(+), we investigated the regulation by beta-NADH of cADPR synthesis and metabolism and the role of cADPR in hypoxic pulmonary vasoconstriction. Significantly higher rates of cADPR synthesis occurred in smooth muscle homogenates of pulmonary arteries, compared with homogenates of systemic arteries. When the beta-NAD(+):beta-NADH ratio was reduced, the net amount of cADPR accumulated increased. This was due, at least in part, to the inhibition of cADPR hydrolase by beta-NADH. Furthermore, hypoxia induced a 10-fold increase in cADPR levels in pulmonary artery smooth muscle, and a membrane-permeant cADPR antagonist, 8-bromo-cADPR, abolished hypoxic pulmonary vasoconstriction in pulmonary artery rings. We propose that the cellular redox state may be coupled via an increase in beta-NADH levels to enhanced cADPR synthesis, activation of ryanodine receptors, and sarcoplasmic reticulum Ca(2+) release. This redox-sensing pathway may offer new therapeutic targets for hypoxic pulmonary hypertension

Factores que influyen en el aprovechamiento de los alumnos de telesecundaria de organización unitaria del estado de Durango, México

Using results from test for 2009 Evaluación National de Logro Academic en Centros Escolares (ENLACE), It is examined the possible gender influence and socioeconomic marginalization level in academic achievement on telesecundaria unitary system (junior high school, mostly rural; It is a television-mediated system) in third-grade students in Durango, México State. Results statistically show that only teacher’s gender has significantly influenced in achievement, while students by female teachers they are who obtained the highest scores. Gender and marginalization level variables were not significantly correlated. It is possible that students with marginalization average levels they may have a better school achievement, but it is necessary to consider a larger sample in order to properly assess this possibility. The fact that students by male teachers obtained lower scores, and possibility that these are more diverse, it would imply that men and women assimilate the teaching-learning process, in normal conditions, in different ways.Utilizando los resultados para 2009 de la prueba de Evaluación Nacional de Logro Académico en Centros Escolares (ENLACE), se examinó la posible influencia del género de los profesores y el grado de marginación de sus comunidades en el aprovechamiento de alumnos de tercer año de telesecundarias de sistema unitario del estado de Durango, México. Los resultados muestran que estadísticamente sólo el género del profesor influyó de manera significativa en el aprovechamiento escolar, siendo los alumnos a cargo de maestras los que obtuvieron los mayores puntajes. Las variables género y grado de marginación no estuvieron significativamente correlacionadas. Es posible que los alumnos de niveles medios de marginación pudieran tener un mejor aprovechamiento escolar, pero es necesario considerar una muestra mayor para poder evaluar adecuadamente esta posibilidad. El hecho de que los alumnos a cargo de maestros hayan obtenido menores puntajes, y la posibilidad de que estos sean más diversos, podría implicar que hombres y mujeres asimilen el proceso enseñanza aprendizaje, en condiciones normales, de manera distinta