20- HETE vasoconstrictor

S)-HETE is a potent chemoattractant for smooth muscle cells, causing migration at concentrations as low as 1 fmol/L it may play a role in myointimal proliferation that occurs after vascular injury such as that caused by angioplasty. Its stereoisomer, 12(K)-HETE, is not a chemoattractant but is a potent inhibitor of the Na+/K+ ATPase in the cornea. LTC4 and LTD4 reduce myocardial contractility and coronary blood flow, leading to cardiac depression. Lipoxin A and lipoxin B seem to exert coronary vasoconstrictor effects. 

Platelets have been shown to cooperate with leukocytes in production of chemotactic fectors which the cells are unable to synthesize themselves. 12-HETE from platelets are metabolized by unstimulated neutrophils to 12,20-di-HETE (Marcus et al, 1984,1988). Leukocytes produces increased amounts of leukotrienes, because 12-HPETE produced in activated platelets stimulates the activity of leukocyte 5-lipoxygenase (Maclouf et al, 1982 Romano and Sethan, 1992). Neutrophils convert arachidonic acid released from stimulated platelets to produce 5-HETE and leukotriene B4 (LTB ) (Marcus et al, 1982). Platelet activating fector (PAF) are shown to stimulate production of LTB from tiiese cells (Lin et al, 1982). Platelets can also produce the vasoconstrictor leukotriene C4 (LTC4) from leukotriene A4 (LTA4) synthesized by leukocytes (Maclouf and Murphy, 1988). Activated platelets and neutrophils release PAF (Lynch and Henson, 1986) which is a potent mediator of inflammation and asthma. 

The mechanism-based inactivator 1-ABT (Section 3.3.5), which is not very selective and inactivates multiple P450 enzymes, including those responsible for the S3mthesis of both EETs and 20-HETE, has also been used, alone or in conjunction with other inhibitors, to assess the role of these metabolites in skeletal muscle angiogenesis induced by electrical stimulation as well as in the renal and vasoconstrictor actions of angiotensin . ... 

Because of their physiological and pathophysiological implications, the vasoactive properties of EETs and 20-HETE are under extensive scrutiny. The consensus is that EETs (5,6-and 11,12-EET in particular) and 20-HETE are powerful vasodilators and vasoconstrictors of small diameter vascular beds, respectively , and that these actions are associated with their ability to inactivate (20-HETE) or activate (EETs) Ca -activated vascular smooth muscle K channels ... 

In addition to LOX-mediated reactions, AA-derived HETEs and LA-derived HODEs can also be biosynthesized by CYP pathways (Bylund et al. 1998). HODEs which have been determined as CYP products include 9-, 13-, and 18-HODE (Bylund et al. 1998), while some work on rodents and primates found the additional products 8-HODE, 11-HODE (acid-labile converts into 9/13-HODE), and 14-HODE (Oliw et al. 1993). 8-HODE, 11-HODE, and 14-HODE were all formed via an allylic hydroxylation, whereas the 9/J-HODE and 131 -HODE were stereoselectively biosynthesized via hydroxylation with double bond migration (Oliw et al. 1993). AA-derived HETEs that can be generated by CYP include 7-, 10-, and 13-HETE (acid-labile) and 5,6-diHETrE. CYP enzymes can also catalyze the formation of terminal and subterminal hydroxylated species such as 16-, 18-, 19-, 20-HETE, all of which have been shown to exhibit vasodilatory properties (Carroll et al. 1996). 19-HETE has been reported to affect vascular tone and ion transport. 20-HETE is a CYP4 family AA oxidation product, which has been found to be a potent vasoconstrictor but it also has been identified in some studies as having a pro-carcinogenic role contributing to cell proliferation and tumor growth (Guo et al. 2008 Alexanian et al. 2009 Liu et al. 2010). 

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