Impaired flow-induced arterial remodeling in DOCA-salt hypertensive rats

Arteries from young healthy animals respond to chronic changes in blood flow and blood pressure by structural remodeling. We tested whether the ability to respond to decreased (-90%) or increased (+100%) blood flow is impaired during the development of deoxycorticosterone acetate (DOCA)-salt hypertension in rats, a model for an upregulated endothelin-1 system. Mesenteric small arteries (MrA) were exposed to low blood flow (LF) or high blood flow (HF) for 4 or 7 weeks. The bioavailability of vasoactive peptides was modified by chronic treatment of the rats with the dual neutral endopeptidase (NEP)/endothelin-converting enzyme (ECE) inhibitor SOL1. After 3 or 6 weeks of hypertension, the MrA showed hypertrophic arterial remodeling (3 weeks: media cross-sectional area (mCSA): 10 +/- 1 x 10(3) to 17 +/- 2 x 10(3) mu m(2); 6 weeks: 13 +/- 2 x 10(3) to 24 +/- 3 x 10(3) mu m(2)). After 3, but not 6, weeks of hypertension, the arterial diameter was increased (empty set: 385 +/- 13 to 463 +/- 14 mu m). SOL1 reduced hypertrophy after 3 weeks of hypertension (mCSA: 6 x 10(3) +/- 1 x 10(3) mu m(2)). The diameter of the HF arteries of normotensive rats increased (empty set: 463 +/- 22 mu m) but no expansion occurred in the HF arteries of hypertensive rats (empty set: 471 +/- 16 mu m). MrA from SOL1-treated hypertensive rats did show a significant diameter increase (empty set: 419 +/- 13 to 475 +/- 16 mu m). Arteries exposed to LF showed inward remodeling in normotensive and hypertensive rats (mean empty set between 235 and 290 mu m), and infiltration of monocyte/ macrophages. SOL1 treatment did not affect the arterial diameter of LF arteries but reduced the infiltration of monocyte/ macrophages. We show for the first time that flow-induced remodeling is impaired during the development of DOCA-salt hypertension and that this can be prevented by chronic NEP/ECE inhibition. Hypertension Research (2012) 35, 1093-1101; doi:10.1038/hr.2012.94; published online 12 July 201

Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension: does selectivity matter?

Treatment options for pulmonary arterial hypertension (PAH) have considerably improved in the past few years. Endothelin (ET)-receptor antagonism has been established as a first-line option for the majority of PAH patients. Endothelin-receptor antagonists (ETRAs) comprise sulfonamide and non-sulfonamide agents with different affinities for ET-receptor subtypes (ETA and ETB), and the focus of development has shifted from drugs with less selectivity to those with high selectivity. There is ongoing debate as to whether selective or non-selective ET-receptor antagonism is more beneficial in the treatment of PAH. This paper reviews the current evidence from experimental and clinical studies obtained from a thorough literature search focusing on the three marketed drugs bosentan, sitaxentan, and ambrisentan. A clinically meaningful difference among the three approved ETRAs with respect to their ET-receptor selectivity could not be demonstrated to date. Therefore, in clinical practice, other features are likely to be of greater relevance when considering treatment, such as the potential for serious drug–drug interactions, convenience of dosing schedule, or rates of limiting side effects. These characteristics bear more relation to the chemical or pharmacological properties of the drugs than to receptor selectivity itself

A Control-Flow Normalization Algorithm and Its Complexity

We present a simple method for normalizing the control-flow of programs to facilitate program transformations, program analysis, and automatic parallelization. While previous methods result in programs whose control flowgraphs are reducible, programs normalized by this technique satisfy a stronger condition than reducibility and are therefore simpler in their syntax and structure than with previous methods. In particular, all control-flow cycles are normalized into single-entry, single-exit while loops, and all goto's are eliminated. Furthermore, the method avoids problems of code replication that are characteristic of node-splitting techniques. This restructuring obviates the control dependence graph, since afterwards control dependence relations are manifest in the syntax tree of the program. In this paper we present transformations that effect this normalization, and study the complexity of the method. Index Terms: Continuations, control-flow, elimination algorithms, normalization,..

Contribution a l'etude des proprietes des composes ternaires intermetalliques de type TM2Si2

SIGLECNRS T 59833 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Restructuration des programmes Fortran en vue de leur parallelisation

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc