20-HETE and Furosemide-Induced Natriuresis in Salt-Sensitive Essential Hypertension

Abstract

Cyclooxygenase metabolites of arachidonic acid modulate the natriuretic effect of furosemide. It is not known whether 20-HETE, a monooxygenase metabolite of arachidonic acid that also inhibits sodium transport, participates in the action of furosemide. We measured urine sodium (UNaV) and 20-HETE during furosemide diuresis (40 mg three times over 12 hours) in 12 salt-sensitive (SS) and 11 salt-resistant (SR), salt-replete hypertensive subjects (126±24 mmol/24 hours positive sodium balance produced by 160-mmol-sodium diet and 2 L saline infusion). Individual systolic blood pressure decreases from the salt-replete to the salt-depleted state were the index of salt-sensitivity. SS had low plasma renin with blunted responses to changes in salt balance, inappropriate plasma aldosterone, and an increased aldosterone/renin ratio. UNaV by furosemide was less in SS (263±25 mmol/12 hours) than in SR (351±25 mmol/12 hours, P <0.02) patients. 20-HETE was not different between SS and SR patients before (1.92±0.38 versus 1.37±0.34 μg/h) or after furosemide (1.52±0.27 versus 2.01±0.40 μg/h), but furosemide changed 20-HETE excretion in opposite direction in SR (0.63±0.26) versus SS (−0.40±0.17, P <0.005) patients. In all patients together, %Δ20-HETE by furosemide correlated with %ΔUNaV ( r =0.56, P <0.01) and negatively with salt-sensitivity of blood pressure ( r =−0.55, P <0.01). In SS, Δ20-HETE by furosemide correlated with Δaldosterone/renin ratio ( r =0.60, P <0.05), whereas 20-HETE during furosemide had a negative correlation with body mass index ( r =−0.73, P <0.01). Our data suggest that 20-HETE modulates the natriuretic response to furosemide, and impaired natriuresis of SS involves a mechanism that alters the 20-HETE response to furosemide and is linked to salt-sensitivity of blood pressure.