de Souza Priscila, da Silva Rita de Cássia Vilhena, da Silva Luisa Mota, Steimbach Viviane Miranda Bispo, Moreno Karyne Garcia Tafarelo, Gasparotto Junior Arquimedes
Graduate Program in Pharmaceutical Sciences, Nucleus of Chemical-Pharmaceutical Investigations (NIQFAR), University of Vale do Itajaí, Itajaí, SC, Brazil.
Laboratory of Electrophysiology and Cardiovascular Pharmacology, Faculty of Health Sciences, Universidade Federal da Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
Evid Based Complement Alternat Med. 2022 Feb 16;2022:4560607. doi: 10.1155/2022/4560607. eCollection 2022.
Boldine, 2,9-dihydroxy-1,10-dimethoxyaporphine, is the main alkaloid found in the leaves and bark of Molina. In recent years, boldine has demonstrated several pharmacological properties that benefit endothelial function, blood pressure control, and reduce damage in kidney diseases. However, the renal vasodilator effects and mechanisms remain unknown. Herein, perfused rat kidneys were used to study the ability of boldine to induce vasodilation of renal arteries. For that, left kidney preparations with and without functional endothelium were contracted with phenylephrine and received 10-300 nmol boldine injections. The preparations were then perfused for 15 min with phenylephrine plus L-NAME, indomethacin, KCl, tetraethylammonium, glibenclamide, apamin, charybdotoxin, or iberiotoxin. In 30, 100, and 300 nmol doses, boldine induced a dose-and endothelium-dependent relaxing effect on the renal vascular bed. No vasodilator effects were observed in preparations lacking functional endothelium. While the inhibition of the cyclooxygenase enzyme through the addition of indomethacin did not cause any change in the vasodilating action of boldine, the nonselective nitric oxide synthase inhibitor L-NAME fully precluded the vasodilatory action of boldine at all doses tested. The perfusion with KCl or tetraethylammonium (nonselective K channels blocker) also abolished the vasodilatory effect of boldine, indicating the participation of K channels in the renal action of boldine. The perfusion with glibenclamide (selective ATP-sensitive K channels blocker), iberiotoxin (selective high-conductance Ca-activated K channel blocker), and charybdotoxin (selective high- and intermediate-conductance Ca-activated K channel blocker) did not modify the vasodilatory action of boldine. On the other hand, the perfusion with apamin (selective small-conductance Ca-activated K channel blocker) completely prevented the vasodilatory action of boldine at all doses tested. Together, the present study showed the renal vasodilatory properties of boldine, an effect dependent on the generation of nitric oxide and the opening of a small-conductance Ca-activated K channel.
波尔定碱，即2,9 - 二羟基 - 1,10 - 二甲氧基阿朴啡，是在莫利纳（Molina）植物的叶子和树皮中发现的主要生物碱。近年来，波尔定碱已展现出多种药理特性，这些特性对内皮功能、血压控制有益，并能减轻肾脏疾病中的损伤。然而，其肾血管舒张作用及机制仍不清楚。在此，使用灌注大鼠肾脏来研究波尔定碱诱导肾动脉血管舒张的能力。为此，对有功能内皮和无功能内皮的左肾制备物用去氧肾上腺素使其收缩，并注射10 - 300 nmol的波尔定碱。然后用去氧肾上腺素加左旋硝基精氨酸甲酯（L - NAME）、吲哚美辛、氯化钾、四乙铵、格列本脲、蜂毒明肽、蝎毒素或iberiotoxin灌注制备物15分钟。在30、100和300 nmol剂量下，波尔定碱对肾血管床产生剂量和内皮依赖性的舒张作用。在缺乏功能内皮的制备物中未观察到血管舒张作用。虽然通过添加吲哚美辛抑制环氧化酶酶并未使波尔定碱的血管舒张作用发生任何改变，但非选择性一氧化氮合酶抑制剂L - NAME在所有测试剂量下完全消除了波尔定碱的血管舒张作用。用氯化钾或四乙铵（非选择性钾通道阻滞剂）灌注也消除了波尔定碱的血管舒张作用，表明钾通道参与了波尔定碱的肾脏作用。用格列本脲（选择性ATP敏感性钾通道阻滞剂）、iberiotoxin（选择性高电导钙激活钾通道阻滞剂）和蝎毒素（选择性高电导和中电导钙激活钾通道阻滞剂）灌注并未改变波尔定碱的血管舒张作用。另一方面，用蜂毒明肽（选择性小电导钙激活钾通道阻滞剂）灌注在所有测试剂量下完全阻止了波尔定碱的血管舒张作用。总之，本研究显示了波尔定碱的肾血管舒张特性，该作用依赖于一氧化氮的生成和小电导钙激活钾通道的开放。
