Omega-3 polyunsaturated fatty acid-induced vasodilation in mouse aorta
and mesenteric arteries is not mediated by ATP-sensitive potassium
channels
Abstract
There is strong evidence that the omega-3 polyunsaturated fatty acids
(n-3 PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)
have cardioprotective effects. n-3 PUFAs cause vasodilation in
hypertensive patients, in part controlled by increased membrane
conductance to potassium. As KATP play a major role in vascular tone
regulation and are involved in hypertension, we aimed to verify whether
n-3 PUFA-mediated vasodilation involved the opening of KATP channels. We
used a murine model in which the KATP channel subunit, Kir6.1, is
deleted in vascular smooth muscle. The vasomotor response of
preconstricted arteries to physiologically relevant concentrations of
DHA and EPA was measured using wire myography, using the channel blocker
PNU-37883A. The effect of n-3 PUFAs on potassium currents in wild-type
native smooth muscle cells was investigated using whole-cell patch
clamping. DHA and EPA induced vasodilation in mouse aorta and mesenteric
arteries; relaxations in the aorta were sensitive to KATP blockade with
PNU-37883A. Endothelium removal didn’t affect relaxation to EPA and
caused a small but significant inhibition of relaxation to DHA. In the
knock-out model, relaxations to DHA and EPA were unaffected by channel
knockdown but were still inhibited by PNU-37883A, indicating that the
action of PNU-37883A on relaxation may not reflect inhibition of KATP.
In native aortic smooth muscle cells DHA failed to activate KATP
currents. We conclude that DHA and EPA cause vasodilation in mouse aorta
and mesenteric arteries. Relaxations in blocker-treated arteries from
knock-out mice demonstrate that KATP channels are not involved in the
n-3 PUFA-induced relaxation.