Comparison of vasodilatory properties of 14,15-EET analogs: structural requirements for dilation
| Autor: | Kamalesh K. Sharma, Y. Krishna Reddy, K. Malla Reddy, Kathryn M. Gauthier, Christine Deeter, William B. Campbell, Sarah B. Hittner, P. Srinagesh Kumar, John R. Falck, U. Murali Krishna |
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| Rok vydání: | 2003 |
| Předmět: |
Endothelium-derived hyperpolarizing factor
Physiology Vasodilator Agents Biological activity Vasodilation Arteries In Vitro Techniques Epoxyeicosatrienoic acid Coronary Vessels Potassium channel Structure-Activity Relationship chemistry.chemical_compound 8 11 14-Eicosatrienoic Acid chemistry Biochemistry Eicosanoid Physiology (medical) cardiovascular system Biophysics Animals Cattle lipids (amino acids peptides and proteins) Arachidonic acid Cardiology and Cardiovascular Medicine |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 284:H337-H349 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00831.2001 |
| Popis: | 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= 10−6M). 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 Δ11 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. |
| Databáze: | OpenAIRE |
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