20-HETE and furosemide-induced natriuresis in salt-sensitive essential hypertension.
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 microg/h) or after furosemide (1.52+/-0.27 versus 2.01+/-0.40 microg/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, %Delta20-HETE by furosemide correlated with %DeltaUNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, Delta20-HETE by furosemide correlated with Deltaaldosterone/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.
Laffer
Cheryl L
CL
Department of Medicine, Lenox Hill Hospital, New York University School of Medicine, New York, USA. claffer@lenoxhill.net
Laniado-Schwartzman
Michal
M
Wang
Mong-Heng
MH
Nasjletti
Alberto
A
Elijovich
Fernando
F
D000328:Adult; D000450:Aldosterone / Q000097:blood; D001794:Blood Pressure; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000652:urine*; D006973:Hypertension / Q000097:blood / Q000209:etiology / Q000652:urine*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine*; D012965:Sodium Chloride / Q000008:administration & dosage*
D006893:Hydroxyeicosatetraenoic Acids; D012965:Sodium Chloride; D000450:Aldosterone; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D005665:Furosemide; D012964:Sodium; D012083:Renin