Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects
We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na /24 hours, HiNa) and depletion (10 mEq Na /24 hours+furosemide 40 mg×3, Lo...
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| Published in: | Hypertension (Dallas, Tex. 1979) Vol. 71; no. 2; p. 346 |
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| Language: | English |
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01.02.2018
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| ISSN: | 1524-4563, 1524-4563 |
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| Abstract | We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na
/24 hours, HiNa) and depletion (10 mEq Na
/24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na
, and Na
/K
ratio for the 3 days of the experiment combined (
<0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na
/K
ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone (
<0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na
/K
ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na
excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications. |
|---|---|
| AbstractList | We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na+/24 hours, HiNa) and depletion (10 mEq Na+/24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na+, and Na+/K+ ratio for the 3 days of the experiment combined (P<0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na+/K+ ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone (P<0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na+/K+ ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na+ excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications.We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na+/24 hours, HiNa) and depletion (10 mEq Na+/24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na+, and Na+/K+ ratio for the 3 days of the experiment combined (P<0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na+/K+ ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone (P<0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na+/K+ ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na+ excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications. We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt sensitive (8) with an inpatient protocol of salt loading (460 mEq Na /24 hours, HiNa) and depletion (10 mEq Na /24 hours+furosemide 40 mg×3, LoNa). No urine EETs were detected; hence, enzyme linked innumosorbent assay 14,15-DHETs (dihydroxyeicosatrienoic acids) were considered the total converted 14,15-urine pool. We report ultra-performance liquid chromatography/tandem mass spectrometry plasma EETs, DHETs, and their sum (plasma total pool) for the 3 regioisomers (8,9-, 11,12-, 14,15-) and their sum (08,15-). In salt-resistant subjects, urine total pool was unchanged by HiNa, decreased by LoNa, and correlated with urine sodium excretion, fractional excretion of Na , and Na /K ratio for the 3 days of the experiment combined ( <0.03). In contrast, plasma total pool increased in LoNa and did not correlate with natriuresis or Na /K ratio but showed correlations between EETs, blood pressures, and catecholamines and between DHETs and aldosterone ( <0.03). Urine total pool of salt-sensitive was lower than that of salt-resistant subjects in certain phases of the experiment, lacked responses to changes in salt balance, and exhibited limited correlations with natriuresis and Na /K ratio during LoNa only. Plasma total pool of salt-sensitive was lower than in salt-resistant subjects and did not correlate with blood pressures or aldosterone but did with catecholamines. We conclude that the urine total pool reflects a renal pool involved in regulation of natriuresis, whereas the plasma total pools are of systemic origin, uninvolved in Na excretion, perhaps contributing to regulation of vascular tone. Data suggest that abnormalities in EETs in salt-sensitive subjects participate in their renal or vascular dysfunction, which has potential therapeutic implications. |
| Author | Laffer, Cheryl L Milne, Ginger L Elijovich, Fernando Brown, Nancy J Laniado-Schwartzman, Michal |
| Author_xml | – sequence: 1 givenname: Fernando surname: Elijovich fullname: Elijovich, Fernando email: fernando.elijovich@vanderbilt.edu organization: From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (F.E., G.L.M., N.J.B., C.L.L.); and Department of Pharmacology, New York Medical College, Valhalla (M.L.-S.). fernando.elijovich@vanderbilt.edu – sequence: 2 givenname: Ginger L surname: Milne fullname: Milne, Ginger L organization: From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (F.E., G.L.M., N.J.B., C.L.L.); and Department of Pharmacology, New York Medical College, Valhalla (M.L.-S.) – sequence: 3 givenname: Nancy J surname: Brown fullname: Brown, Nancy J organization: From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (F.E., G.L.M., N.J.B., C.L.L.); and Department of Pharmacology, New York Medical College, Valhalla (M.L.-S.) – sequence: 4 givenname: Michal surname: Laniado-Schwartzman fullname: Laniado-Schwartzman, Michal organization: From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (F.E., G.L.M., N.J.B., C.L.L.); and Department of Pharmacology, New York Medical College, Valhalla (M.L.-S.) – sequence: 5 givenname: Cheryl L surname: Laffer fullname: Laffer, Cheryl L organization: From the Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN (F.E., G.L.M., N.J.B., C.L.L.); and Department of Pharmacology, New York Medical College, Valhalla (M.L.-S.) |
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| CitedBy_id | crossref_primary_10_1016_j_ebiom_2021_103331 crossref_primary_10_1016_j_ijchy_2020_100048 crossref_primary_10_1016_j_freeradbiomed_2019_05_012 crossref_primary_10_1161_HYPERTENSIONAHA_120_14808 crossref_primary_10_1161_HYPERTENSIONAHA_123_21285 crossref_primary_10_1016_j_pharmthera_2018_06_015 crossref_primary_10_1097_CRD_0000000000000834 crossref_primary_10_1161_HYPERTENSIONAHA_121_16495 |
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| Keywords | blood pressure salt sensitive CYP450 eicosanoids catecholamines aldosterone |
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| Snippet | We measured epoxyeicosatrienoic acids (EETs) and dihydroxyeicosatrienoic acids (DHETs) in 21 normotensive subjects classified as salt resistant (13) or salt... |
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| SubjectTerms | 8,11,14-Eicosatrienoic Acid - metabolism Adult Aldosterone - blood Blood Pressure - physiology Catecholamines - blood Chromatography, Liquid Eicosanoids Enzyme-Linked Immunosorbent Assay Female Humans Male Natriuresis - physiology Sodium Chloride, Dietary - metabolism Tandem Mass Spectrometry |
| Title | Two Pools of Epoxyeicosatrienoic Acids in Humans: Alterations in Salt-Sensitive Normotensive Subjects |
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