Increased levels of 12(S)-HETE in patients with essential hypertension.
The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of arachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], which is reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabolites exhibit a variety of biological activities such as mediation of angiotensin II-induced intracellular calcium transients in cultured rat vascular smooth muscle cells. It has recently been reported that platelet 12(S)-HETE production is enhanced in the spontaneously hypertensive rat. The pronounced hypotensive effect of LO inhibition in SHR suggests that LO activity may play a role in this form of hypertension. The aim of this study was to determine the basal and thrombin-induced platelet 12(S)-HETE production and the urinary 12(S)-HETE excretion in essential hypertension. We studied 19 patients with this disease (57+/-2 years of age) and 9 normotensive control subjects (48+/-5 years of age) (P:=0.074). 12(S)-HETE was measured in Sep-Pack-extracted samples with specific ELISA and high-performance liquid chromatography. The platelet basal level of 12(S)-HETE was significantly higher in patients than in control subjects (3.56+/-1.22 versus 0.64+/-0.13 ng/10(6) platelets, P:<0.025). In contrast, there were no differences in thrombin-stimulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients versus 4.87+/-1.46 in control subjects (P:=0.61). Platelet 12-LO protein levels, measured by Western blotting with a polyclonal antibody, were higher in the patients than in the control subjects. The urinary excretion of 12(S)-HETE was higher in patients than in control subjects: 36.8+/-7.24 versus 17.1+/-3.14 ng/mg creatinine (P:<0.01). These results indicate that 12(S)-HETE levels and 12-LO protein are increased in patients with essential hypertension, suggesting a role for this metabolite in human hypertension.
Servicio de Nefrología, Laboratorio de Hormonología (D.G.-N., F.R.), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain.
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González-Núñez
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Claria
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Rivera
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Poch
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood* / Q000652:urine; D000328:Adult; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood*; D008297:Male; D008875:Middle Aged
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001092:Arachidonate 12-Lipoxygenase