Increased levels of 12(S)-HETE in patients with essential hypertension

The platelet-type 12-lipoxygenase (12-LO) catalyzes the transformation of a rachidonic acid into 12-hydroperoxyeicosatetraenoic acid [12-(S)HPETE], whi ch is reduced to 12-hydroxyeicosatetraenoic acid [12-(S)HETE]. These metabo lites exhibit a variety of biological activities such as mediation of angio tensin II-induced intracellular calcium transients in cultured rat vascular smooth muscle cells. It has recently been reported that platelet 12(S)-HET E production is enhanced in the spontaneously hypertensive rat. The pronoun ced hypotensive effect of LO inhibition in SHR suggests that LO activity ma y play a role in this form of hypertension. The aim of this study was to de termine the basal and thrombin-induced platelet 12(S)-HETE production and t he urinary 12(S)-HETE excretion in essential hypertension. We studied 19 pa tients with this disease (57+/-2 years of age) and 9 normotensive control s ubjects (48+/-5 years of age) (P=0.074). 12(S)-HETE was measured in Sep-Pac k-extracted samples with specific ELISA and high-performance liquid chromat ography. 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-st imulated (1 U/mL) 12(S)-HETE generation: 7.66+/-2.14 in patients versus 4.8 7+/-1.46 in control subjects (P=0.61). Platelet 12-LO protein levels, measu red by Western blotting with a polyclonal antibody, were higher in the pati ents 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 a nd 12-LO protein are increased in patients with essential hypertension, sug gesting a role for this metabolite in human hypertension.