20-HETE relaxes bovine coronary arteries through the release of prostacyclin

Phillip F. Pratt, J R Falck, Komandla M. Reddy, Jason B. Kurian, William B. Campbell

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Neutrophils respond to ischemic injury by infiltrating the myocardium via the vascular wall. During this process, neutrophils are activated and release inflammatory mediators. Some of these mediators are metabolites of arachidonic acid. We have reported that neutrophils metabolize arachidonic acid to 20-HETE, a cytochrome P450 metabolite. We investigated the effects of 20-HETE on coronary vascular tone by examining 20-HETE-induced changes in isometric tension in bovine coronary artery rings precontracted with the thromboxane-mimetic, U46619. 20-HETE relaxed precontracted coronary rings in a concentration-dependent manner (EC50 of 3 X 10-7 mol/L). Pretreatment with indomethacin, a cyclooxygenase inhibitor, shifted the concentration- response curve to the right (EC50 of 1 X 10-6 mol/L); maximal relaxations were not affected. This suggested that 20-HETE-induced relaxations were, in part, dependent on the cyclooxygenase pathway. Relaxations to 20-HETE were not significantly changed in endothelium-denuded rings. To determine whether metabolism of 20-HETE to a vasoactive compound might explain the relaxations caused by 20-HETE, rings of coronary artery were incubated with [3H] 20- HETE. The incubation buffer was extracted and the [3H] products resolved on reverse-phase HPLC. Both denuded and intact arteries failed to metabolize [3H] 20-HETE. To investigate whether 20-HETE-induced relaxations were related to release of prostacyclin, we measured the release of 6-keto PGF(1a), the stable metabolite of prostacyclin, from bovine coronary arteries. 20-HETE (1 X 10-6 mol/L) stimulated an increase in 6-keto PGF(1a) in intact vessels (908 ± 138 pg/mL versus 1402 ± 157 pg/mL, basal versus stimulated). Thus, 20-HETE-induced relaxations are due, in part, to the stimulation of the release of the dilatory prostanoid, prostacyclin.

Original languageEnglish (US)
Pages (from-to)237-241
Number of pages5
JournalHypertension
Volume31
Issue number1 II SUPPL.
StatePublished - Jan 1998

Fingerprint

Epoprostenol
Coronary Vessels
Neutrophils
Prostaglandins F
Arachidonic Acid
20-hydroxy-5,8,11,14-eicosatetraenoic acid
Blood Vessels
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Cyclooxygenase Inhibitors
Thromboxanes
Prostaglandin-Endoperoxide Synthases
Indomethacin
Cytochrome P-450 Enzyme System
Prostaglandins
Endothelium
Myocardium
Buffers
Arteries
High Pressure Liquid Chromatography

Keywords

  • Coronary artery
  • Cyclooxygenase
  • Cytochrome P
  • Endothelium
  • Neutrophils
  • Prostacyclin

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Pratt, P. F., Falck, J. R., Reddy, K. M., Kurian, J. B., & Campbell, W. B. (1998). 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension, 31(1 II SUPPL.), 237-241.

20-HETE relaxes bovine coronary arteries through the release of prostacyclin. / Pratt, Phillip F.; Falck, J R; Reddy, Komandla M.; Kurian, Jason B.; Campbell, William B.

In: Hypertension, Vol. 31, No. 1 II SUPPL., 01.1998, p. 237-241.

Research output: Contribution to journalArticle

Pratt, PF, Falck, JR, Reddy, KM, Kurian, JB & Campbell, WB 1998, '20-HETE relaxes bovine coronary arteries through the release of prostacyclin', Hypertension, vol. 31, no. 1 II SUPPL., pp. 237-241.
Pratt PF, Falck JR, Reddy KM, Kurian JB, Campbell WB. 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. Hypertension. 1998 Jan;31(1 II SUPPL.):237-241.
Pratt, Phillip F. ; Falck, J R ; Reddy, Komandla M. ; Kurian, Jason B. ; Campbell, William B. / 20-HETE relaxes bovine coronary arteries through the release of prostacyclin. In: Hypertension. 1998 ; Vol. 31, No. 1 II SUPPL. pp. 237-241.
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