{'fraction_non_alphanumeric': 0.029874572405929306, 'fraction_numerical': 0.007525655644241733, 'mean_word_length': 5.125698324022347, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
l‐arginine transport and sepsis

THE practicing anaesthesiologist encounters several inflammatory conditions where alterations in the L-arginine/nitric oxide (NO) pathway are a part of the disease process. In sepsis, NO production is markedly increased and is considered to be a key component in the cardiovascular collapse seen in septic shock. Normally, this tiny gas molecule participates in a variety of homeostatic activities such as control of vascular tone, modulation of nerve transmission and regulation of the activity of various proteins and enzymes. This is achieved by the constitutive production of NO by calcium-dependent NO-synthases (NOSs) in, e.g. the vascular endothelium (endothelial NOS, eNOS) and nerves (neuronal NOS, nNOS). NO is produced from the cationic, semi-essential amino acid L-arginine and molecular oxygen in a complicated fiveelectron oxidation process yielding equimolar amounts of NO and L-citrulline. Bacterial products, e.g. lipopolysaccharide (LPS) and certain cytokines are capable of inducing the production of NO from a third type of NOS (inducible NOS, iNOS). This calcium-independent enzyme produces large amounts of NO which may kill bacteria, fungus and tumour cells, but may also induce excessive vasodilation and nitrosative stress to host tissues. NO overproduction has been shown to interfere in mitochondrial respiration and to induce apoptosis and necrosis. Therefore, the ‘overproduction’ of NO during inflammation and sepsis is a doubled-edged sword which has been extensively debated in the literature (1). During the last decades there has been a considerable scientific and industrial interest in trying to find pharmacological tools to intervene in the NO-system in order to treat inflammatory conditions. Such tools may interfere at several levels of the NOsystem: modulation of substrate availability, blockade of nuclear transcription factors, NOS inhibition, NO scavenging or inhibition of target compound activity, e.g. soluble guanylylcyclase and cGMP. Transport of amino acids such as L-arginine across the cell membrane is regulated by a variety of different transporter systems (2). The system yþ is the principal cationic amino acid transport system expressed in NO-producing cells. Within the yþ system, there are four related cationic amino acid transport (CAT) proteins identified (CAT-1 to CAT-4, with two additional splice variants of CAT-2; CAT-2A and CAT-2B). The CAT isoforms are the main transporters of L-arginine across the cell membrane and therefore of special interest in NO biology. CAT-2B expression is increased by cytokines and LPS making it particularly interesting in relation to sepsis. The nuclear transcription factor-kB (NF-kB) is involved in this process and is also active in induction of iNOS. Hence, concomitant induction of CAT-2B together with iNOS will provide substrate availability to this high-output enzyme. These events have previously been shown in endothelial and smooth muscle cells, macrophages and peripheral blood mononuclear cells from patients with sepsis. Obviously, these transport proteins are putative targets for intervention in the L-arginine/NO pathway in sepsis and other inflammatory diseases. In this issue of Acta Anesthesiolgica Scandinavica, Yang and coworkers have used an in vivo rat model to investigate regulatory mechanisms behind the expression of the CATs in relation to LPS stimulation and NO production (3). This group has published a series of articles in recent years depicting the regulatory mechanisms behind LPS-induced CAT expression, one of which was published earlier this year in Acta Anesthesiologia Scandinavica (4). In that article their focus was on the rat lung where a co-induction of iNOS, CAT-2 and CAT-2B by LPS was associated with increased production of NO. These events were also associated with signs of pulmonary injury. Pretreatment with inhibitors of NF-kB, e.g. dexamethasone attenuated induction of iNOS, CAT-2 and CAT2B and reduced lung injury. In the present study, a similar rat model was used but this time the liver was in focus. In contrast to the lung, the CAT proteins were constitutively expressed in rat liver and CAT-2 and CAT-2B mRNA concentrations actually Acta Anaesthesiol Scand 2005; 49: 434—436 Copyright # Acta Anaesthesiol Scand 2005 Printed in UK. All rights reserved ACTA ANAESTHESIOLOGICA SCANDINAVICA