Effect of 14,15-epoxyeicosatrienoic acid infusion on blood pressure in normal and hypertensive rats.
Intravenous (IV) and intraarterial (IA) infusion of 14,15-epoxyeicosatrienoic acid (14,15-EET) produced a dose-dependent decrease in mean arterial blood pressure (MAP) in normal and spontaneously hypertensive rats (SHR). The hypotensive effect of 14,15-EET was observed from 1 microgram/kg to 10 micrograms/kg with a maximum reduction in MAP as much as 45 +/- 6 mmHg in both normal and SHR. In normal rats the hypotensive effect was found to be more pronounced when 14,15-EET was infused IA than IV. This suggests that 14,15-EET may be metabolized as it passes through the lungs. However, in SHR there was no difference in MAP when 14,15-EET was infused either IA or IV. This indicates that there is a differential removal of the epoxide across the pulmonary circulation. Administration of indomethacin failed to inhibit the hypotensive action of 14,15-EET, suggesting that it may not be a cyclo-oxygenase dependent mechanism. However, the PAF antagonist of BN-52021 inhibited the hypotensive action of 14,15-EET. This therefore, suggests that the release of PAF may be involved in the hypotensive action of this epoxide of arachidonic acid.
Lin
W K
WK
Department of Physiology and Medicine, New York Medical College, Valhalla 10595.
Falck
J R
JR
Wong
P Y
PY
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D046934:Ginkgolides; D006973:Hypertension / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007536:Isomerism; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012016:Reference Values
D000959:Antihypertensive Agents; D004224:Diterpenes; D005231:Fatty Acids, Unsaturated; D046934:Ginkgolides; D007783:Lactones; D010936:Plant Extracts; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; C045856:ginkgolide B; D015126:8,11,14-Eicosatrienoic Acid; D007213:Indomethacin