5-hydroxy-6-8-11-14-eicosatetraenoic-acid and 20-hydroxy-5-8-11-14-eicosatetraenoic-acid

Post-exercise hypotension (PEH) is the phenomenon of lowered blood pressure after a single bout of exercise. Only a fraction of people develops PEH but its occurrence correlates well with long-term effects of sports on blood pressure. Therefore, PEH has been suggested as a suitable predictor for the effectivity of exercise as therapy in hypertension. Local vascular bioactive lipids might play a potential role in this context. We performed a cross-over clinical pilot study with 18 healthy volunteers to investigate the occurrence of PEH after a single short-term endurance exercise. Furthermore, we investigated the plasma lipid profile with focus on arachidonic acid (AA)-derived metabolites as potential biomarkers of PEH. A single bout of ergometer cycling induced a significant PEH in healthy volunteers with the expected high inter-individual variability. Targeted lipid spectrum analysis revealed significant upregulation of several lipids in the direct post-exercise phase. Among these changes, only 15- hydroxyeicosatetranoic acid (HETE) correlated significantly with the extent of PEH but in an AA-independent manner, suggesting that 15-HETE might act as specific PEH-marker. Our data indicate that specific lipid modulation might facilitate the identification of patients who will benefit from exercise activity in hypertension therapy. However, larger trials including hypertonic patients are necessary to verify the clinical value of this hypothesis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Arachidonic Acid; Biological Variation, Population; Blood Pressure; Cross-Over Studies; Dinoprostone; Exercise; Female; Healthy Volunteers; Heart Rate; Humans; Hydroxyeicosatetraenoic Acids; Hypertension; Lipid Metabolism; Male; Pilot Projects; Post-Exercise Hypotension; Thromboxanes

The periparturient period of dairy cows is characterized by intense lipolysis in adipose tissues (AT), which induces the release of free fatty acids (FFA) into circulation. Among FFA, polyunsaturated fatty acids are susceptible to oxidation and can modulate inflammatory responses during lipolysis within AT. Linoleic and arachidonic acid oxidized products (oxylipids) such as hydroxy-octadecadienoic acids (HODE) and hydroxy-eicosatetraenoic acids (HETE), were recently identified as products of lipolysis that could modulate AT inflammation during lipolysis. However, the effect of lipolysis intensity during the transition from gestation to lactation on fatty acid substrate availability and subsequent AT oxylipid biosynthesis is currently unknown. We hypothesized that in periparturient dairy cows, alterations in AT and plasma fatty acids and oxylipid profiles coincide with changes in lipolysis intensity and stage of lactation. Blood and subcutaneous AT samples were collected from periparturient cows at -27±7 (G1) and -10±5 (G2) d prepartum and at 8±3 d postpartum (PP). Targeted lipidomic analysis was performed on plasma and AT using HPLC-MS/MS. We report that FFA concentrations increased as parturition approached and were highest at PP. Cows exhibiting high lipolysis rate at PP (FFA>1.0 mEq/L) had higher body condition scores at G1 compared to cows with low lipolysis rate (FFA<1.0 mEq/L). Concentrations of plasma linoleic and arachidonic acids were increased at PP. In AT, 13-HODE, and 5-, 11- and 15-HETE were increased at PP compared to G1 and G2. Concentrations of beta hydroxybutyrate were positively correlated with those of 13-HODE and 15-HETE in AT. Plasma concentrations of 5- and 20-HETE were increased at PP. These data demonstrate that prepartum adiposity predisposes cows to intense lipolysis post-partum and may exacerbate AT inflammation because of increased production of pro-inflammatory oxylipids including 5- and 15-HETE and 13-HODE. These results support a role for certain linoleic and arachidonic acid-derived oxylipids as positive and negative modulators of AT inflammation during periparturient lipolysis.

Topics: Adipose Tissue; Animals; Cattle; Chromatography, High Pressure Liquid; Dairying; Female; Hydroxyeicosatetraenoic Acids; Lipolysis; Parturition; Pregnancy; Tandem Mass Spectrometry

Active metabolites of arachidonic acid (AA), eicosanoids, strongly influence renal homeostasis. The aims of this study were to measure perioperative variations in lipoxygenase (LOX)-derived 5-, 12- and 15-hydroxyeicosatetraenoic (HETE) acids levels, and to examine whether (i) dynamics of these eicosanoid generation changes during the first 5 min of renal allograft reperfusion, (ii) examined HETE acids may influence perioperative 20-HETE generation, and (iii) LOX HETE may serve as perioperative markers of early post-transplant allograft function.. Sixty-nine kidney recipients were divided into early, slow and delayed graft function (EGF, SGF and DGF, respectively) groups. Blood was taken directly before, and in the consecutive minutes of graft reperfusion. HETE concentrations were measured using liquid chromatography. Creatinine levels were measured during the perioperative period, as well as during follow-up visits (first post-transplant year).. Our results demonstrated significant differences in the concentrations and dynamics of HETE changes between the examined groups. Moreover, observed changes in HETE concentrations were strongly associated with post-transplant graft function and perioperative 20-HETE synthesis. Application of cut-off limits for newly introduced markers, that is 71.72 ng/mL for 5-HETE(5), 12.3 ng/mL for 12-HETE△(5-0) and -6.1 ng/mL for 15-HETE△(5-0), resulted in 72.5-81.5% sensitivity and 50-54% specificity for SGF/DGF prediction. Moreover, mixed model analysis revealed that recipients classified according to results of 5-HETE(5) and 15-HETE△(5-0) significantly differ in 1-year post-transplant allograft function (P  =  0.03 and P  < 0.05, respectively), however, not in the frequency of acute rejections' episodes (P = 0.91 and P = 0.31, respectively).. We hereby report that human kidney transplantations are accompanied by significant changes in LOX AA metabolism, which strongly influences and predicts early (1 year) post-transplant graft function.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Adult; Arachidonic Acid; Biomarkers; Female; Graft Survival; Humans; Hydroxyeicosatetraenoic Acids; Kidney Transplantation; Lipoxygenase; Male; Middle Aged; Perioperative Period; Retrospective Studies; Time Factors; Transplantation, Homologous

Arachidonic acid metabolites such as prostaglandins, thromboxanes, and leukotrienes are well known modulators of intestinal vascular perfusion, motility, and electrogenic ion transport. We investigated the effect of different hydroxyeicosatetraenoic acids (HETEs) from cytochrome P450- and lipoxygenase-dependent arachidonate metabolism on electrogenic chloride secretion in rat distal colon. Using conventional Ussing techniques, basolateral 12-HETE significantly decreased basal short-circuit current (I(sc)) and inhibited furosemide-sensitive Cl(-) secretion stimulated by either dibutyryl cAMP, prostaglandin E(2), or theophylline in a concentration-dependent manner (IC(50) = 1.5 nM). These data were underlined by significant inhibition of J(net)(Cl) in unidirectional (36)Cl flux measurements. Direct regulation of the basolateral Na(+)-K(+)-2Cl(-) cotransporter or the Na-K-ATPase could be excluded because 12-HETE had no effect on furosemide-sensitive K(+) secretion induced by epinephrine, or ouabain-sensitive Na(+) reabsorption stimulated by aldosterone. Inhibitors of Ca(2+)-activated and voltage-gated K(+) channels such as apamin, charybdotoxin, and dendrotoxin did not affect secretagogue-dependent I(sc) and its regulation by 12-HETE. In contrast, glibenclamide significantly attenuated the effect of 12-HETE on secretagogue-induced I(sc), whereas chromanol 293B, an inhibitor of cAMP-dependent K(+) conductance, had an additive effect. We speculate that 12-HETE, like glibenclamide, affects intestinal Cl(-) secretion by inhibiting basolateral K(+)(ATP) channels. In contrast to these findings, neither 5-HETE nor 20-HETE had any effect on basal I(sc) or cAMP-dependent Cl(-) secretion.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Bucladesine; Chlorides; Colon; Furosemide; Hydroxyeicosatetraenoic Acids; Male; Ouabain; Potassium; Potassium Channel Blockers; Rats; Rats, Wistar; Sodium