(Hypertension. 2001;37:334.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Increased Levels of 12(S)-HETE in Patients With Essential Hypertension
From Servicio de Nefrología (D.G.-N., E.P.), Unidad de DNA (J.C.), Laboratorio de Hormonología (D.G.-N., F.R.), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain.
Correspondence to Dr Esteban Poch, Servicio de Nefrología, Hospital Clinic, Universidad de Barcelona, Villarroel 170, 08036 Barcelona, Spain. E-mail epoch{at}medicina.ub.es
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/106 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.
Key Words: arachidonic acid • hypertension, essential • lipoxygenase • thrombin
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