Number of nitrate groups determines reactivity and potency of organic nitrates: a proof of concept study in ALDH-2−/− mice

Background and purpose: Mitochondrial aldehyde dehydrogenase (ALDH-2) has been shown to provide a pathway for bioactivation of organic nitrates and to be prone to desensitization in response to highly potent, but not to less potent, nitrates. We therefore sought to support the hypothesis that bioactivation by ALDH-2 critically depends on the number of nitrate groups within the nitrovasodilator. Experimental approach: Nitrates with one (PEMN), two (PEDN; GDN), three (PETriN; glyceryl trinitrate, GTN) and four (pentaerithrityl tetranitrate, PETN) nitrate groups were investigated. Vasodilatory potency was measured in isometric tension studies using isolated aortic segments of wild type (WT) an…

A new class of organic nitrates: investigations on bioactivation, tolerance and cross-tolerance phenomena

Background and purpose:  The chronic use of organic nitrates is limited by serious side effects including oxidative stress, nitrate tolerance and/or endothelial dysfunction. The side effects and potency of nitroglycerine depend on mitochondrial aldehyde dehydrogenase (ALDH-2). We sought to determine whether this concept can be extended to a new class of organic nitrates with amino moieties (aminoalkyl nitrates). Experimental approach:  Vasodilator potency of the organic nitrates, in vitro tolerance and in vivo tolerance (after continuous infusion for 3 days) were assessed in wild-type and ALDH-2 knockout mice by isometric tension studies. Mitochondrial oxidative stress was analysed by L-012…

P105. New findings on vasodilator potency, tachyphylaxis, and bioavailability of organic nitrates reveal: The tolerance-devoid clinical action of pentaerithrityl tetranitrate (PETN) is produced by its metabolites PEdiN and PEmonoN

NO donors. Part 16: investigations on structure-activity relationships of organic mononitrates reveal 2-nitrooxyethylammoniumnitrate as a high potent vasodilator.

The vasoactive properties of 14 organic mononitrates were investigated in vitro using PGF(2alpha)-precontracted porcine pulmonary arteries. A surprisingly wide range of vasorelaxant potencies was observed (pD(2): 3.36-7.50). Activities showed to be highly sensitive to the molecular structure and the substituents at the molecular carrier of the nitrate group. A correlation between lipophilicity and vasorelaxant potency could not be recognized. 2-Nitrooxyethylammoniumnitrate (1) was found to be slightly superior to the high potency trinitrate GTN.

The Contingent Negative Variation – An Electrophysiological Correlate of Temporal Processing or Reference Memory?

Abstract In EEG research, the contingent negative variation (CNV) is considered to be strongly related to interval timing (e.g., Macar & Vidal, 2004 ; Macar, Vidal, & Casini, 1999). However, it is discussed controversially whether certain properties of the CNV (e.g., amplitude, peak latency and resolution) directly reflect the process of temporal accumulation or rather processes related to reference memory or decision stages in temporal information processing (van Rijn et al., 2011). This present study was designed in order to investigate the relationship between CNV mean amplitude, CNV resolution, and memory processes as well as processes of temporal accumulation. The task design aimed at …