Gendviliene Vida, Zablockaite Danguole, Gurskaite Herta, Martisiene Irma, Stankevicius Antanas
Institute of Cardiology, Kaunas University of Medicine, Sukileliu 17, 50161 Kaunas, Lithuania.
Medicina (Kaunas). 2006;42(10):829-35.
The aim of the study was to investigate the effects of 2-aminopyridine (2-AP) and its new sulfonylcarbamide derivatives AP21, AP22, AP26, and AP27 (10(-(5))-10(-(3)) M) on pinacidil (5x10(-(5)) M), an activator of K(ATP) channels, induced shortening of action potential duration and reduction of contraction force in guinea pig papillary muscles. Experiments were carried out using a standard method of myocardium electromechanical activity registration. Under control conditions (perfusion of papillary muscles with Tyrode solution), an average of action potential duration (APD), measured at 90% (APD(90)) and 50% (APD(50)) of repolarization, were 211.78+/-8.6 ms and 173.22+/-8.3 ms (n=18), respectively, and contraction force was 1.77+/-0.36 mN (n=18). Pinacidil markedly decreased APD(90) to 58.16+/-4.4%, APD(50) - to 52.51+/-4.85% (n=18), and contraction force - to 30.45+/-4.06% (n=18), (p<0.001) vs. control. 2-aminopyridine and its sulfonylcarbamide derivative AP22 (with 4-toluolsulfonylcarbamide fragment and methyl iodide-quaternized nitrogen of the pyridine ring) had no effect on the pinacidil-induced shortening of action potential and reduction of contraction force. 2-aminopyridine derivatives, AP21 (with 4-toluolsulfonylcarbamide fragment) and AP26 (with allyl bromide-quaternized nitrogen of the pyridine ring), showed a weak effect on pinacidil-induced shortening of action potential duration. The 2-aminopyridine derivative AP27 (with the 4-toluolsulfonylcarbamide fragment where nitrogen of the pyridine ring was quaternized by 4-nitrobenzyl bromide) had the most potent stimulatory effect on action potential duration and contraction force, which were reduced by pinacidil.
本研究旨在探讨2-氨基吡啶（2-AP）及其新的磺酰脲衍生物AP21、AP22、AP26和AP27（10⁻⁵ - 10⁻³ M）对豚鼠乳头肌中钾离子通道开放剂吡那地尔（5×10⁻⁵ M）诱导的动作电位时程缩短和收缩力降低的影响。实验采用心肌机电活动记录的标准方法进行。在对照条件下（用台氏液灌注乳头肌），在复极化90%（APD₉₀）和50%（APD₅₀）时测量的动作电位时程平均值分别为211.78±8.6 ms和173.22±8.3 ms（n = 18），收缩力为1.77±0.36 mN（n = 18）。与对照组相比，吡那地尔显著降低APD₉₀至58.16±4.4%，APD₅₀至52.51±4.85%（n =
18），收缩力降至30.45±4.06%（n = 18），（p < 0.001）。2-氨基吡啶及其磺酰脲衍生物AP22（具有对甲苯磺酰脲片段且吡啶环氮原子被甲基碘季铵化）对吡那地尔诱导的动作电位缩短和收缩力降低没有影响。2-氨基吡啶衍生物AP21（具有对甲苯磺酰脲片段）和AP26（吡啶环氮原子被烯丙基溴季铵化）对吡那地尔诱导的动作电位时程缩短有微弱影响。2-氨基吡啶衍生物AP27（具有对甲苯磺酰脲片段，吡啶环氮原子被4-硝基苄基溴季铵化）对被吡那地尔降低的动作电位时程和收缩力具有最显著的刺激作用。
