Characterization of potassium channels involved in the mechanisms of vascular relaxation induced by omega‐3 polyunsaturated fatty acids in rat arteries; a critical role for KATP channels

Abstract

IntroductionFish oils are involved in the vasodilation of arteries and studies indicate that the main components involved are omega‐3 polyunsaturated fatty acids (n‐3 PUFA) that include docosahexaenoic acid (DHA) and eicosapentaenoic acids (EPA) (1). We previously demonstrated that inhibition of KCa channels partially attenuates fish oil mediated relaxation in rat mesenteric arteries (2). Since a considerable proportion of the relaxation to n‐3 PUFA was residual to blockade of KCa, vasodilation pathways involving other types of potassium channels could be involved. Studies report that the predominant vasodilation mechanisms can differ depending upon the type of artery an (3). Therefore, our main objective was to investigate these pathways in n‐3 PUFA‐induced relaxation of both large muscular (aorta) and resistance rat arteries (mesenteric).Methods2mm segments of rat arteries were mounted on a wire myograph and cumulative concentration response curves to DHA or EPA (10nM–30μM) mediated relaxation were examined following pre‐constriction with U46619 (10–500nM) in rat aorta and mesenteric artery. In certain experiments isotonic Krebs solution containing high [KCl] (final bath concentration 30mM; inhibits hyperpolarization mediated by potassium channels) or PNU37883A (3μM), a KATP blocker were administered prior to assessing relaxation. Relaxation was expressed as mean % relaxation of U46619‐induced constriction ± SEM of n animals. Data was analysed using one‐way ANOVA with Bonferroni's post‐test. P‐value of ≤ 0.05 was considered as being statistically significant.ResultsNon‐selective inhibition of potassium channels with high [KCl] Krebs virtually abolished both DHA‐ and EPA‐induced relaxation in rat aorta. Furthermore, High [KCl] Krebs also partially inhibited relaxation mediated by both DHA and EPA in rat mesenteric artery. Inhibition of KATP with PNU37883A attenuated fish oil‐induced relaxation in rat aorta. Consistently, in rat mesenteric artery PNU37883A also inhibited both DHA‐ and EPA‐induced relaxation.ConclusionsWe demonstrate that the non‐selective blockade of potassium channels abolished both DHA‐ and EPA‐mediated relaxation of rat aorta. Furthermore, inhibition of potassium channels in the resistance mesenteric artery also inhibited relaxation induced by DHA and EPA. We further characterised the potassium channels involved; blockade of KATP channels inhibited both DHA and EPA induced relaxation in rat aorta and mesenteric artery. This is the first study indicating that DHA and EPA evoke relaxation through KATP in both rat large muscular and resistance arteries. We will incorporate patch clamp in our future studies to investigate whether n‐3 PUFA directly regulate KATP channels.Support or Funding InformationThis work was supported by British Heart Foundation (PhD Studentship no. FS/14/33/30799)