Description
Electrolyte and fluid transport in the kidney are regulated in part by arachidonic acid and its metabolites. (±)16-
HETE is the racemic version of a minor CYP450 metabolite of arachidonic acid released by the kidney upon angiotensin II stimulation. The biological activity of 16-
HETE is stereospecific. 16(R)-
HETE dose-
dependently stimulates vasodilation of the rabbit kidney, however 16(S)-
HETE does not affect perfusion pressure. At a concentration of 2 μM the (S)-
enantiomer of 16-
HETE inhibits proximal tubule ATPase activity by as much as 60%, whereas the (R)-
isomer has negligible effects on ATPase activity.
Uses
16-HETE is arachidonic acid metabolite through subterminal hydroxylation by cytochrome P-450. 16-HETE exhibits vasodilatory and PMN inhibitory effects and serves as biomarker for early stages of non-alcoholic fatty liver disease[1][2][3].
Definition
ChEBI: A HETE that consists of arachidonic acid bearing an additional hydroxy substituent at position 16.
in vivo
16-HETE (1-20 μg, i.a.) is stereospecificially involved in vasodilation, regulation of renal perfusion and in mechanisms of tubular transport with S- enantiomer in New Zealand white rabbit[2].
16-HETE (1 μg/kg/min) suppresses the increase of intracranial pressure (ICP) in a rabbit model of thromboembolic stroke[1].
| Animal Model: | New Zealand White rabbit[2] |
| Dosage: | 1-20 μg |
| Administration: | injection into artery |
| Result: | 16S inhibited 60% ATPase activity at the concentration of 2 μM, while 16R enantiomer remained inactive. |
| Animal Model: | New Zealand White rabbit[1] |
| Dosage: | 1 μg/kg/min |
| Administration: | 6 hours constant infusion from Hours 1 to 2 after autologous clot embolization |
| Result: | Reduced infarction area and less increased ICP. |
References
[1] Bednar MM, et al., 16(R)-hydroxyeicosatetraenoic acid, a novel cytochrome P450 product of arachidonic acid, suppresses activation of human polymorphonuclear leukocyte and reduces intracranial pressure in a rabbit model of thromboembolic stroke. Neurosurgery. 2000 Dec;47(6):1410-8; discussion 1418-9. PMID:11126912
[2] Carroll MA, e al., Cytochrome P-450-dependent HETEs: profile of biological activity and stimulation by vasoactive peptides. Am J Physiol. 1996 Oct;271(4 Pt 2):R863-9. DOI:
10.1152/ajpregu.1996.271.4.R863[3] Maciejewska D, et al., Metabolites of arachidonic acid and linoleic acid in early stages of non-alcoholic fatty liver disease--A pilot study. Prostaglandins Other Lipid Mediat. 2015 Sep;121(Pt B):184-9. DOI:
10.1016/j.prostaglandins.2015.09.003
