Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am J Physiol 1992 Aug;263(2 Pt 2):H519-25
Date
08/01/1992Pubmed ID
1510149DOI
10.1152/ajpheart.1992.263.2.H519Scopus ID
2-s2.0-0026758963 (requires institutional sign-in at Scopus site) 289 CitationsAbstract
Microsomal preparations of cat brain incubated with [14C]arachidonic acid produced epoxyeicosatrienoic acids (EETs) that eluted with the same retention times as synthetically prepared 5,6-, 8,9-, and 11,12-EETs. These compounds dilated serotonin-preconstricted, pressurized cat cerebral arteries in a dose-dependent fashion. Epoxide formation was not found in mitochondrial fractions and was dependent on the presence of NADPH. The maximum effects of 8,9-EET and 11,12-EET were greater than those of 5,6-EET. The cellular basis of this vasodilation was further investigated by examining the effects of 8,9-EET and 11,12-EET on K+ channel activity in vascular muscle cells freshly isolated from cat cerebral arteries. Both 8,9-EET and 11,12-EET increased the frequency of opening, mean open time, and open-state probability of a 98-pS K+ channel recorded in the cell-attached mode with 145 mM KCl in the pipette and 4.7 mM KCl in the bath. Blockade of K+ channel activity with tetraethylammonium attenuated the vasodilatory effects of 11,12-EET on serotonin-preconstricted cat cerebral arteries. These results suggest that endogenously formed EETs may participate in local regulation of cerebral blood flow by dilating cerebral arteries through a mechanism that involves activation of K+ channels.
Author List
Gebremedhin D, Ma YH, Falck JR, Roman RJ, VanRollins M, Harder DRMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Arachidonic Acid
Brain
Cats
Cerebral Arteries
Electrophysiology
Female
In Vitro Techniques
Male
Microsomes
Muscle, Smooth, Vascular
Potassium
Potassium Channels
Vasodilator Agents