This Article Full Text Full Text (PDF) All Versions of this Article: 41/3/703    most recent 01.HYP.0000051888.91497.47v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laffer, C. L. Articles by Elijovich, F. Search for Related Content PubMed PubMed Citation Articles by Laffer, C. L. Articles by Elijovich, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB FUROSEMIDE SODIUM SODIUM CHLORIDE Medline Plus Health Information High Blood Pressure Related Collections Other hypertension Clinical Studies Other Research

(Hypertension. 2003;41:703.)
© 2003 American Heart Association, Inc.

Scientific Contributions

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

Cheryl L. Laffer; Michal Laniado-Schwartzman; Mong-Heng Wang; Alberto Nasjletti; Fernando Elijovich

From the Department of Medicine, Lenox Hill Hospital, New York University School of Medicine (C.L.L., F.E.), New York; and Department of Pharmacology, New York Medical College (M.L.-S., M.W., A.N.), Valhalla.

Correspondence to Dr Cheryl Laffer, Hypertension and Cardiovascular Center, 210 E 64th St, New York, NY 10021. E-mail claffer{at}lenoxhill.net

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, %20-HETE by furosemide correlated with %UNaV (r=0.56, P<0.01) and negatively with salt-sensitivity of blood pressure (r=-0.55, P<0.01). In SS, 20-HETE by furosemide correlated with aldosterone/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.

Key Words: hypertension, sodium dependent • natriuresis • furosemide • arachidonic acid • sodium • human • risk factors

This article has been cited by other articles:

				C. Fava, M. Montagnana, P. Almgren, L. Rosberg, G. Lippi, B. Hedblad, G. Engstrom, G. Berglund, P. Minuz, and O. Melander The V433M Variant of the CYP4F2 Is Associated With Ischemic Stroke in Male Swedes Beyond Its Effect on Blood Pressure Hypertension, August 1, 2008; 52(2): 373 - 380. [Abstract] [Full Text] [PDF]

				C. L. Laffer, J. V. Gainer, M. R. Waterman, J. H. Capdevila, M. Laniado-Schwartzman, A. Nasjletti, N. J. Brown, and F. Elijovich The T8590C Polymorphism of CYP4A11 and 20-Hydroxyeicosatetraenoic Acid in Essential Hypertension Hypertension, March 1, 2008; 51(3): 767 - 772. [Abstract] [Full Text] [PDF]

				D. E. Stec, R. J. Roman, A. Flasch, and M. J. Rieder Functional polymorphism in human CYP4F2 decreases 20-HETE production Physiol Genomics, June 19, 2007; 30(1): 74 - 81. [Abstract] [Full Text] [PDF]

				C. Kirchheimer, C. F. Mendez, A. Acquier, and S. Nowicki Role of 20-HETE in D1/D2 dopamine receptor synergism resulting in the inhibition of Na+-K+-ATPase activity in the proximal tubule Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1435 - F1442. [Abstract] [Full Text] [PDF]

				T. Vera, M. Taylor, Q. Bohman, A. Flasch, R. J. Roman, and D. E. Stec Fenofibrate Prevents the Development of Angiotensin II-Dependent Hypertension in Mice Hypertension, April 1, 2005; 45(4): 730 - 735. [Abstract] [Full Text] [PDF]

				I. Fleming Cytochrome P-450 Under Pressure: More Evidence for a Link Between 20-Hydroxyeicosatetraenoic Acid and Hypertension Circulation, January 4, 2005; 111(1): 5 - 7. [Full Text] [PDF]

				J. V. Gainer, A. Bellamine, E. P. Dawson, K. E. Womble, S. W. Grant, Y. Wang, L. A. Cupples, C.-Y. Guo, S. Demissie, C. J. O'Donnell, et al. Functional Variant of CYP4A11 20-Hydroxyeicosatetraenoic Acid Synthase Is Associated With Essential Hypertension Circulation, January 4, 2005; 111(1): 63 - 69. [Abstract] [Full Text] [PDF]

				M. H. Weinberger More on the Sodium Saga Hypertension, November 1, 2004; 44(5): 609 - 611. [Full Text] [PDF]

				C. L. Laffer, M. Laniado-Schwartzman, A. Nasjletti, and F. Elijovich 20-HETE and Circulating Insulin in Essential Hypertension With Obesity Hypertension, February 1, 2004; 43(2): 388 - 392. [Abstract] [Full Text] [PDF]

				K. M. Hoagland, A. K. Flasch, and R. J. Roman Inhibitors of 20-HETE Formation Promote Salt-Sensitive Hypertension in Rats Hypertension, October 1, 2003; 42(4): 669 - 673. [Abstract] [Full Text] [PDF]