Platelets arachidonic acid metabolism in patients with essential hypertension

Abstract

Arachidonic acid's (AA) metabolites, eicosanoids, exert a tremendous influence on circulatory and vascular homeostasis, and in humans are generated by many organs and cell types. In this study we wanted to verify whether platelets AA metabolism play a significant role in pathogenesis of essential hypertension (EH). Participants were divided into the study (EH) and the control group. Plasma and urine concentrations of isoprostanes (8-iPF(2alpha)-III) and thromboxane B(2) (TxB(2)) were determined using the ELISA method. The levels of 5- and 12-hydroxyeicosatetraenoic (HETE) acids, generated by platelets, were analysed using RP-HPLC. In a suspension of not stimulated and AA-stimulated platelets TxB(2) level was statistically lower in the study than in the control group (p < 0.0001 and 0.001 respectively). The concentration of 12-HETE was significantly elevated in EH patients compared to the control group; however, only in the non-stimulated conditions (p < 0.05). Plasma and urine F2-isoprostanes levels were significantly higher in hypertensive individuals than in the control group (p < 0.00002 and p < 0.01 respectively). Moreover, EH patients excreted more TxB(2) in urine than normotensive individuals (p < 0.05). Our results highlight the mutual connections between the platelets AA metabolism and indicate its possible role in the pathogenesis of arterial hypertension. Moreover, we hypothesize that platelets AA metabolism may exert a pro-atherosclerotic effect. Finally, we suggest the use of (5-HETE+12-HETE)/TxB(2) parameter in further studies.

Platelet activation in hypertension associated with hypercholesterolemia: effects of irbesartan

“…Besides NAD(P)H oxidase, mitochondria and COX-1, other molecules are likely to be involved in ROS generation, such as 12lipoxygenase, cPLA 2 and PKC. Recently, it was reported that platelet AA metabolism exerts a proatherosclerotic effect [38]. In our study, PLA 2 and 12-lipoxygenase protein expressions were found to be increased in the platelets isolated from the HH group, confirming the contribution of these molecules to ROS generation in combined hypertension-hypercholesterolemia.…”

Effect of Soluble Epoxide Hydrolase on the Modulation of Coronary Reactive Hyperemia: Role of Oxylipins and PPARγ

“…In human umbilical artery smooth muscle cells, 11-HETE inhibited vascular smooth muscle cell proliferation [54], whereas in the isolated Guinea Pig lungs, 5- and 15-HETEs produced vasoconstriction and edema [55]. Also, the generation of mid-chain HETEs is increased in essential hypertension [56] suggesting that they could be involved in its pathogenesis. These reports point to opposite effects of EETs and HETEs in vascular biology.…”

Analysis of bioactive eicosanoids in equine plasma by stable isotope dilution reversed‐phase liquid chromatography/multiple reaction monitoring mass spectrometry

“…Results of other studies also showed that the major source of endogenously derived AA are platelets and that translocation of cPLA 2 from the cytosol to the membrane releases AA from membrane phospholipids, [57] and produces (AE)-12-HETE and TXB 2 as major metabolites. [58,59] The results of this study show increased production of (AE)-9-HETE, (AE)-12-HETE, (AE)-15-HETE, LTB 4 , LTE 4 and TXB 2 in CI A23187-treated equine whole blood which could have been formed from platelets containing endogenous source of AA. Pretreatment of equine whole blood with DEX, an inducer of a protein which inhibits cPLA 2 , resulted in a significant reduction in all HETEs, LTs and TBX synthesis.…”