Navran S S, Adair S E, Jemelka S K, Seidel C L, Allen J C
Department of Medicine, Baylor College of Medicine, Houston.
J Pharmacol Exp Ther. 1988 May;245(2):608-13.
The effects of alpha-1 and alpha-2 selective adrenergic agents on sodium pump activity were investigated in intact canine femoral artery and saphenous vein by measuring ouabain-sensitive uptake of 86Rb. In both vessels, the alpha-1-selective agonist, phenylephrine, stimulated 86Rb uptake in a dose-dependent manner. The uptake was blocked by prazosin and yohimbine with the order of potency: prazosin greater than yohimbine. The alpha-2-selective agonist, clonidine, also stimulated 86Rb uptake in the saphenous vein but not in the femoral artery. The stimulation was blocked by prazosin and yohimbine with the order of potency: yohimbine greater than prazosin. The potency of phenylephrine to contract saphenous vein or femoral artery was the same as that for stimulation of ouabain-sensitive 86Rb uptake. Clonidine was 10-fold more potent as a contractile agonist than as a Na+ pump stimulant. It caused only a weak contraction in the femoral artery. Reducing extracellular sodium abolished the stimulation of 86Rb uptake by both phenylephrine and clonidine in saphenous vein. Subsequently it was shown that both agonists increased intracellular sodium levels and these increases were blocked by the alpha receptor antagonists, prazosin and yohimbine, with the same selectivity as was observed in the 86Rb uptake experiments. Sodium pump stimulation produced by both phenylephrine and clonidine was blocked by amiloride. These observations suggest that the activity of the vascular sodium pump can be regulated by both alpha-1 and alpha-2 adrenergic receptors and that the mechanism involves an influx of sodium, most likely through a stimulation of Na+/H+ exchange.
通过测量哇巴因敏感的⁸⁶Rb摄取，研究了α-1和α-2选择性肾上腺素能药物对完整犬股动脉和隐静脉钠泵活性的影响。在这两种血管中，α-1选择性激动剂去氧肾上腺素以剂量依赖方式刺激⁸⁶Rb摄取。哌唑嗪和育亨宾可阻断这种摄取，其效力顺序为：哌唑嗪大于育亨宾。α-2选择性激动剂可乐定也刺激隐静脉中的⁸⁶Rb摄取，但不刺激股动脉。这种刺激被哌唑嗪和育亨宾阻断，效力顺序为：育亨宾大于哌唑嗪。去氧肾上腺素使隐静脉或股动脉收缩的效力与刺激哇巴因敏感的⁸⁶Rb摄取的效力相同。可乐定作为收缩激动剂的效力比作为钠泵刺激剂的效力强10倍。它在股动脉中仅引起微弱收缩。降低细胞外钠可消除去氧肾上腺素和可乐定对隐静脉中⁸⁶Rb摄取的刺激。随后发现，两种激动剂均增加细胞内钠水平，且这些增加被α受体拮抗剂哌唑嗪和育亨宾阻断，其选择性与在⁸⁶Rb摄取实验中观察到的相同。去氧肾上腺素和可乐定产生的钠泵刺激被氨氯地平阻断。这些观察结果表明，血管钠泵的活性可由α-1和α-2肾上腺素能受体调节，其机制可能涉及钠的内流，很可能是通过刺激Na⁺/H⁺交换实现的。
