Carrier G O, Peters T, Bishop V S
J Pharmacol Exp Ther. 1975 Apr;193(1):218-31.
Pyridine aldoxime methochloride (2-PAM) increased the force of contraction of stimulated rabbit left atria in vitro. The threshold concentration was 2.3 times 10- minus 3 M whereas 9.2 times 10- minus 2 M produced the absolute maximum increase in tension of 83%. Pretreatment of rabbits with reserpine (2.5 mg/kg/day for 3 days) had no significant influence on the positive inotropic action of 2-PAM. In addition, propranolol (10- minus 8 and 10- minus 6 M) had no effect. Time to peak tension and the time to complete relaxation during each contraction cycle was significantly prolonged. 2-PAM increased the isometric tension developed by isolated aortic strips. The maximum tension developed by the control aortas to 2-PAM was 1.54 plus or minus 0.17 g and after 10- minus 6 M phentolamine, it remained 1.46 plus or minus 0.19 g. The rate of tension decline of stimulated atria was increased in the presence of 2-PAM from 49.7 plus or minus 2.40 to 28.50 plus or minus 1.32 seconds when the atria were placed in a low calcium (Ca)-containing Ringer's solution (0.24 mM CaCl2). When the bathing medium was changed from a low Ca (0.24 mM CaCl2) Ringer's back to normal Ca (2.4 mM CaCl2) Ringers solution, 2-PAM had no influence on the rate of recovery of the initial tension response of the atria. The 34-Ca uptake and efflux studies demonstrated that 2-PAM had no influence on the inward movement of Ca through the membrane but increased the rate of efflux during the phase II process. 2-PAM depressed the rate of uptake of 45-Ca by the isolated rabbit sarcoplasmic reticulum. The T1/2 for the control uptake was 1.80 plus or minus 0.07 minutes and in the presence of 2-PAM (2 times 10- minus 2, 5 times 10- minus 2, 1 times 10- minus 1 M) the T1/2 was increased to 4.50 plus or minus 0.22, 7.20 plus or minus 0.36 and 11.6 plus or minus 0.44 minutes, respectively. It is concluded from these studies that 2-PAM has a positive inotropic effect on isolated rabbit atria which is probably not related to the autonomic nervous system. The evidence obtained strongly suggests that the mechanism of the positive inotropic action is related to the effect of 2-PAM on the homeostasis of intracellular Ca storage sites.
氯解磷定（2 - PAM）可增强体外刺激的兔左心房的收缩力。阈浓度为2.3×10⁻³ M，而9.2×10⁻² M可使张力绝对最大增加83%。用利血平（2.5 mg/kg/天，共3天）预处理兔子，对2 - PAM的正性肌力作用无显著影响。此外，普萘洛尔（10⁻⁸和10⁻⁶ M）也无作用。每个收缩周期达到张力峰值的时间和完全松弛的时间显著延长。2 - PAM可增加离体主动脉条产生的等长张力。对照主动脉对2 - PAM产生的最大张力为1.54±0.17 g，在加入10⁻⁶ M酚妥拉明后，仍为1.46±0.19 g。当心房置于低钙（Ca）的林格氏液（0.24 mM CaCl₂）中时，在2 - PAM存在下，刺激心房的张力下降速率从49.7±2.40秒增加到28.50±1.32秒。当浴液从低钙（0.24 mM CaCl₂）林格氏液换回正常钙（2.4 mM CaCl₂）林格氏液时，2 - PAM对心房初始张力反应的恢复速率无影响。³⁴Ca摄取和流出研究表明，2 - PAM对Ca通过膜的内向移动无影响，但增加了II期过程中的流出速率。2 - PAM抑制离体兔肌浆网对⁴⁵Ca的摄取速率。对照摄取的T1/2为1.80±0.07分钟，在2 - PAM（2×10⁻²、5×10⁻²、1×10⁻¹ M）存在下，T1/2分别增加到4.50±0.22、7.20±0.36和11.6±0.44分钟。从这些研究得出结论，2 - PAM对离体兔心房有正性肌力作用，这可能与自主神经系统无关。所获得的证据有力地表明，正性肌力作用的机制与2 - PAM对细胞内钙储存部位稳态的影响有关。
