Spironolactone reduces aortic stiffness via blood pressure-dependent effects of canrenoate

Spironolactone is thought to improve aortic stiffness via blood pressure (BP) independent (antifibrotic) effects, but the exact mechanism is unknown. We used metabolomics and hemodynamic measures to reveal the underlying actions of spironolactone in people with a hypertensive response to exercise (HRE). Baseline and follow-up serum samples from 115 participants randomized to 3 months spironolactone (25 mg/day) or placebo were analysed using liquid chromatography/mass spectrometry and nuclear magnetic resonance spectroscopy. Hemodynamic measures recorded at baseline and follow-up included aortic pulse wave velocity (stiffness) and 24 h ambulatory BP. Aortic stiffness was significantly reduced by spironolactone compared with placebo (−0.18 ± 0.17 vs 0.30 ± 0.16 m/s; p 0.05 for all). However, the spironolactone metabolite canrenoate was associated with the change in daytime systolic BP (r = −0.355, p = 0.017) and 24 h pulse pressure (r = −0.332, p = 0.026). This remained highly significant on multiple regression and was independent of age, body mass index and sex. Canrenoate appears to be an active metabolite with BP-dependent effects on the attenuation of aortic stiffness in people with HRE. This finding, together with the lack of change in endogenous metabolites, suggests that the antifibrotic effects of spironolactone could be BP-dependent

The concise guide to PHARMACOLOGY 2013/14: overview

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands, which provides more detailed views of target and ligand properties from the IUPHAR database. This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.<p></p> It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.<p></p&gt

Hydrocarbon Accumulation Analysis by Reconstructing the Canyon-Fill Sequence using Seismic Stratigraphic Interpretation in the Central Gulf Coastal Plain of Texas

The Texas Gulf region has been extensively studied and explored due to its high volume of oil and gas accumulation. One of the most highly productive sequences in the region is the lower Wilcox Group, which was deposited during a gradually sea level rising. The high rate of Tertiary sedimentary source influx and repeatedly transgression and regression resulted in numerous reservoirs and ideal traps. Regression caused the development of incised canyon systems, and later the canyon was filled with marine shales during the transgression. The complex canyon-fill sequence makes petroleum accumulation possible. Both stratigraphic and structural trapping mechanisms are found in the study area. The stratigraphy of the Wilcox Group is divided based on the lithological data and electric logs. In order to investigate the lateral variations of erosional sequences and the distributions of thin-bed sand bodies, we correlate the well logging across the survey. The seismic sequences and related sandstones are identified on the seismic sections after the well-to-seismic tie. Finally, the complex canyon-fill system is rebuilt and the hydrocarbon accumulation pattern is analyzed by conducting seismic stratigraphic interpretation in the study area