Department of Veterinary Pharmacology & Toxicology, College of Veterinary Science & Animal Husbandry, Pandit Deen Dayal Upadhyaya Veterinary Sciences University, Mathura, Uttar Pradesh, India.
Hum Exp Toxicol. 2012 Jun;31(6):579-87. doi: 10.1177/0960327111417909. Epub 2011 Aug 15.
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.
在本研究中，我们评估了二十碳五烯酸（EPA）对绵羊肺动脉钠钾 ATP 酶的影响。动脉环急性（30 分钟）和长期（24 小时）暴露于 EPA（30 μM）显著降低了氯化钾（KCl）诱导的松弛，这是功能性钠钾 ATP 酶活性的指标。在急性暴露中，KCl 诱导松弛的 pD2 和 E max（最大反应）值分别为 3.21 ± 0.33 和 61.58 ± 11.30%（n = 5），而对照组为 3.58 ± 0.07 和 82.44 ± 2.36%（n = 24）。在器官培养中，暴露于 EPA 24 小时的动脉环中 KCl 诱导松弛的 pD2 和 E max 值分别为 2.52 ± 0.11 和 55.00 ± 5.72%，而对照组为 3.04 ± 0.19 和 80.74 ± 11.96%；n = 4。在器官培养中，动脉环暴露于 EPA（30 μM）24 小时，显著降低（17.58 ± 2.15%）α1 同工型钠钾 ATP 酶的蛋白表达。急性暴露于 EPA 30 分钟可显著降低（21.06 ± 5.89%）无机磷（Pi）释放所测的钠钾 ATP 酶活性。EPA 最高至 100 μM 浓度仅轻度（<80mM KCl 收缩的 10%）增加肺动脉的基础张力。此外，EPA（10-30 μM）对 Mg2+-ATPase 活性和环鸟苷单磷酸（cGMP）的产生无影响。所有这些结果表明，EPA 对绵羊肺动脉钠钾 ATP 酶有抑制作用，但长期暴露对钠泵没有额外作用，EPA 诱导的钠钾 ATP 酶抑制可能是由于 α1 同工型钠钾 ATP 酶的蛋白表达减弱所致，而与 cGMP 产生无关。
