Shock Induction by Arterial Hypoperfusion of the Gut Involves Synergistic Interactions between the Peripheral Enkephalin and Nitric Oxide Systems

To determine whether critical splanchnic artery hypoperfusion can provoke systemic shock and to identify the roles of the peripheral opioid and nitric oxide (NO) systems in this process, various degrees of superior mesenteric artery hypoperfusion (SMA-H) were produced in anesthetized adult rabbits (n=40), and hemodynamic and metabolic indices were measured. Metabolic acidosis and irreversible hypodynamic shock occurred with SMA-H at levels representing 25–20% of mean baseline SMA blood flow. In 112 other rabbits subjected to SMA-H at 20% (SMA-H20%), we studied plasma NO and enkephalin (ENK) levels, cardiovascular reactivity to selected physiological agonists, effects of ENKs on plasma NO levels, and effects of peripheral opioid receptor blockade and inducible NO synthase (iNOS) inhibition. SMA-H20% progressively increased systemic blood levels of NO and ENKs. Exogenous ENK administration accentuated SMA-H20%-induced increases in plasma NO levels, and their cardiovascular depressing effects were significantly greater when they were administered during SMA-H20% (vs. administration under baseline conditions). Selective blockade of cardiovascular δ-opioid receptors improved hemodynamics, prevented shock irreversibility and reduced plasma NO levels; similar effects were obtained by selective iNOS inhibition. These findings demonstrate that critical arterial hypoperfusion of the gut can induce hypodynamic systemic shock through ENK-induced hyperactivation of cardiovascular δ-opioid receptors, which leads to increased plasma levels of NO related in part to increased iNOS activity. Since pronounced splanchnic artery hypoperfusion occurs in all advanced systemic shock states, selective δ-opioid receptor antagonists and/or iNOS inhibitors may prove to be useful in improving shock hemodynamics and metabolic derangements and/or preventing progression toward irreversibility

Terpene Specialized Metabolism in Arabidopsis thaliana

Terpenes constitute the largest class of plant secondary (or specialized) metabolites, which are compounds of ecological function in plant defense or the attraction of beneficial organisms. Using biochemical and genetic approaches, nearly all Arabidopsis thaliana (Arabidopsis) enzymes of the core biosynthetic pathways producing the 5-carbon building blocks of terpenes have been characterized and closer insight has been gained into the transcriptional and posttranscriptional/translational mechanisms regulating these pathways. The biochemical function of most prenyltransferases, the downstream enzymes that condense the C5-precursors into central 10-, 15-, and 20-carbon prenyldiphosphate intermediates, has been described, although the function of several isoforms of C20-prenyltranferases is not well understood. Prenyl diphosphates are converted to a variety of C10-, C15-, and C20-terpene products by enzymes of the terpene synthase (TPS) family. Genomic organization of the 32 Arabidopsis TPS genes indicates a species-specific divergence of terpene synthases with tissue- and cell-type specific expression profiles that may have emerged under selection pressures by different organisms. Pseudogenization, differential expression, and subcellular segregation of TPS genes and enzymes contribute to the natural variation of terpene biosynthesis among Arabidopsis accessions (ecotypes) and species. Arabidopsis will remain an important model to investigate the metabolic organization and molecular regulatory networks of terpene specialized metabolism in relation to the biological activities of terpenes