Comparison of vasodilatory properties of 14,15-EET analogs: Structural requirements for dilation

J R Falck, U. Murali Krishna, Y. Krishna Reddy, P. Srinagesh Kumar, K. Malla Reddy, Sarah B. Hittner, Christine Deeter, Kamalesh K. Sharma, Kathryn M. Gauthier, William B. Campbell

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs) are endothelium-derived eicosanoids that activate potassium channels, hyperpolarize the membrane, and cause relaxation. We tested 19 analogs of 14,15-EET on vascular tone to determine the structural features required for activity. 14,15-EET relaxed bovine coronary arterial rings in a concentration-related manner (ED50 = 10-6 M). Changing the carboxyl to an alcohol eliminated dilator activity, whereas 14; 15-EET-methyl ester and 14,15-EET- methylsulfonimide retained full activity. Shortening the distance between the carboxyl and epoxy groups reduced the agonist potency and activity. Removal of all three double bonds decreased potency. An analog with a Δ8 double bond had full activity and potency. However, the analogs with only a Δ5 or Α11 double bond had reduced potency. Conversion of the epoxy oxygen to a sulfur or nitrogen resulted in loss of activity. 14(S),15(R)-EET was more potent than 14(R),15(S)-EET, and 14,15-(cis)-EET was more potent than 14,15-(trans)-EET. These studies indicate that the structural features of 14,15-EET required for relaxation of the bovine coronary artery include a carbon-1 acidic group, a Δ8 double bond, and a 14(S),15(R)-(cis)-epoxy group.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume284
Issue number1 53-1
StatePublished - Jan 1 2003

Fingerprint

Dilatation
14,15-epoxy-5,8,11-eicosatrienoic acid
Eicosanoids
Potassium Channels
Sulfur
Endothelium
Blood Vessels
Coronary Vessels
Esters
Nitrogen
Carbon
Alcohols
Oxygen
Acids
Membranes

Keywords

  • Arachidonic acid
  • Cytochrome P-450
  • Endothelium-derived hyperpolarizing factor
  • Epoxyeicosatrienoic acid

ASJC Scopus subject areas

  • Physiology

Cite this

Falck, J. R., Krishna, U. M., Reddy, Y. K., Kumar, P. S., Reddy, K. M., Hittner, S. B., ... Campbell, W. B. (2003). Comparison of vasodilatory properties of 14,15-EET analogs: Structural requirements for dilation. American Journal of Physiology - Heart and Circulatory Physiology, 284(1 53-1).

Comparison of vasodilatory properties of 14,15-EET analogs : Structural requirements for dilation. / Falck, J R; Krishna, U. Murali; Reddy, Y. Krishna; Kumar, P. Srinagesh; Reddy, K. Malla; Hittner, Sarah B.; Deeter, Christine; Sharma, Kamalesh K.; Gauthier, Kathryn M.; Campbell, William B.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 284, No. 1 53-1, 01.01.2003.

Research output: Contribution to journalArticle

Falck, JR, Krishna, UM, Reddy, YK, Kumar, PS, Reddy, KM, Hittner, SB, Deeter, C, Sharma, KK, Gauthier, KM & Campbell, WB 2003, 'Comparison of vasodilatory properties of 14,15-EET analogs: Structural requirements for dilation', American Journal of Physiology - Heart and Circulatory Physiology, vol. 284, no. 1 53-1.
Falck, J R ; Krishna, U. Murali ; Reddy, Y. Krishna ; Kumar, P. Srinagesh ; Reddy, K. Malla ; Hittner, Sarah B. ; Deeter, Christine ; Sharma, Kamalesh K. ; Gauthier, Kathryn M. ; Campbell, William B. / Comparison of vasodilatory properties of 14,15-EET analogs : Structural requirements for dilation. In: American Journal of Physiology - Heart and Circulatory Physiology. 2003 ; Vol. 284, No. 1 53-1.
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