Effects of epoxyeicosatrienoic acids on volume-activated chloride channels via cyclic GMP pathway in rat mesenteric artery

Abstract

Epoxyeicosatrienoic acids (EETs) are one of the proposed candidates of EDHF. It is known that volume-activated chloride channels (VACCs) play important roles in regulating cell membrane potential, so we hypothesize that VACCs may be involved in EETs-induced vasorelaxation. Rat mesenteric arteries were dissected out and the arteries rings were relaxed by acetylcholine (ACh, 1 nM to 1 mM) in the presence of L-NAME and indomethacin. It was of interest to note that the ACh (1 µM)-induced relaxation was reduced by about 60% when the arteries were precontracted by 60 mM KCl instead of phenylephrine (1 µM). In addition, the ACh (1 µM)-induced relaxations were almost abolished by EETs antagonist (14, 15 epoxyeicosa-5(Z)-enoic acid, 1 µM). Whole cell patch clamping demonstrated that VACC currents in primary cultured rat mesenteric arterial smooth muscle cells were partly inhibited by EETs. However, the inhibition effects were abolished by cyclic GMP (cGMP) antagonists (Rp-cGMP, 100 µM), and cGMP-dependent protein kinase inhibitors (KT-5823, 0.3 µM). Our results suggest that EETs-induced relaxations of mesenteric arteries were partly mediated by inhibition of VACCs through cGMP pathway. (Supported by the Research Grant Council of Hong Kong)