Lipids stimulate the production of 6-keto-prostaglandin F in human dorsal hand veins

Adetola Haastrup, Crystal A. Gadegbeku, Da Zhang, Yurii V. Mukhin, Eddie L. Greene, Ayad A. Jaffa, Brent M. Egan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Obese hypertensives have increased nonesterified fatty acids (NEFAs) and α-adrenergic vascular reactivity. Raising NEFAs locally with intralipid and heparin augments dorsal hand venoconstrictor responses to phenylephrine, an α-adrenoceptor agonist. The enhanced venoconstrictor responses were reversed by indomethacin. The findings suggest that raising NEFAs leads to the generation of cyclooxygenase (COX) product(s) that enhance vascular reactivity. To test this notion, 6-keto-PGF and TxB2, the stable metabolites of prostaglandin H2 (PGH2); prostacyclin (PGI2); and thromboxane (TxA2), were measured ≈1.5 to 2 cm downstream of a dorsal hand vein infusion of intralipid and heparin (n=10) or saline and heparin (n=5) for 2 hours each. During the third hour, intralipid and heparin (experimental) and saline and heparin (control) were continued, and either saline (control) or indomethacin (intervention) were infused. Intralipid and heparin raised local 6-keto PGF concentrations by 350% to 500% (P<0.005), but saline and heparin did not (P=NS). TxB2 levels did not change significantly with any infusion. Infusion of indomethacin during the third hour of intralipid and heparin lowered plasma 6-keto-PGF (P<0.05), whereas infusion of saline with intralipid and heparin did not (P=NS). Oleic and linoleic acids at 100 μmol/L, increased 6-keto-PGF in vascular smooth muscle cells (VSMCs) through a protein kinase C and extracellular, signal-regulated kinase independent pathway. However, oleic and linoleic acids increased intracellular Ca2+ in VSMCs. The data indicate that NEFAs induce the production of COX products, perhaps via Ca2+-dependent activation of phospholipase A2. The COX product(s) may contribute to increased vascular α-adrenergic reactivity among insulin-resistant individuals when NEFAs are elevated.

Original languageEnglish (US)
Pages (from-to)858-863
Number of pages6
JournalHypertension
Volume38
Issue number4
DOIs
StatePublished - 2001

Keywords

  • Cyclooxygenase
  • Fatty acids
  • Muscle, vascular, smooth
  • Prostaglandins

ASJC Scopus subject areas

  • Internal Medicine

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