Evaluation of effects of eicosapentaenoic acid on Na⁺-K⁺-ATPase in sheep pulmonary artery.

In the present study, we have evaluated the effects of eicosapentaenoic acid (EPA) on Na(+)-K(+)-ATPase in sheep pulmonary artery. Acute (30 min) and prolonged (24 h) exposure of arterial rings to EPA (30 μM) significantly decreased potassium chloride (KCl)-induced relaxation, an index of functional Na(+)-K(+)-ATPase activity. In acute exposure, the pD(2) and E (max) (the maximal response) values for KCl-induced relaxation were 3.21 ± 0.33 and 61.58 ± 11.30% (n = 5) versus control 3.58 ± 0.07 and 82.44 ± 2.36% (n = 24), respectively. The pD(2) and E (max) values for KCl-induced relaxation in arterial rings exposed to EPA for 24 h in organ culture were 2.52 ± 0.11 and 55.00 ± 5.72% versus control 3.04 ± 0.19 and 80.74 ± 11.96%, respectively; n = 4. Exposure of the arterial rings to EPA (30 μM) for 24 h in organ culture, significantly decreased (17.58 ± 2.15%) the protein expression of α(1) isoform of Na(+)-K(+)-ATPase. Acute exposure to EPA for 30 min significantly decreased (21.06 ± 5.89%) the Na(+)-K(+)-ATPase activity as measured by inorganic phosphate (Pi) release. EPA, up to 100 μM concentration, marginally (<10% of 80 mM KCl contraction) increased the basal tone of the pulmonary artery. Additionally, EPA (10-30 μM) had no effect on Mg(2+)-ATPase activity as well as on cyclic guanosine monophosphate (cGMP) production. All these results show that EPA has inhibitory effect on Na(+)-K(+)-ATPase in sheep pulmonary artery but prolonged exposure had no additional effect on sodium pump, and EPA-induced inhibition of Na(+)-K(+)-ATPase may be due to attenuation in protein expression of α(1) isoform of Na(+)-K(+)-ATPase independent of cGMP production.