Laboratório de Biofísica do Coração, Departamento de Fisiologia, Universidade Federal de Sergipe, Aracaju, SE, Brazil.
Eur J Pharmacol. 2011 Dec 15;672(1-3):135-42. doi: 10.1016/j.ejphar.2011.09.186. Epub 2011 Oct 10.
The present study aimed to investigate the inotropic effects of R(+)-pulegone, a monoterpene found in plant species belonging to the genus Mentha, on the mammalian heart. In electrically stimulated guinea pig atria, R(+)-pulegone reduced the contractile force (~83%) and decreased the contraction time measured at 50% of the maximum force amplitude (CT(50)) from 45.8 ± 6.2 ms to 36.9 ± 6.2 ms, suggesting that R(+)-pulegone may have an effect on Ca(2+) homeostasis. Nifedipine (40 μM), taken as a positive control, showed a very similar profile. To explore the hypothesis that R(+)-pulegone is somehow affecting Ca(2+) handling, we determined concentration-response curves for both CaCl(2) and BAY K8644. R(+)-pulegone shifted these curves rightward. Using isolated mouse ventricular cardiomyocytes, we measured whole-cell L-type Ca(2+) current and observed an I(Ca,L) peak reduction of 13.7 ± 2.5% and 40.2 ± 2.9% after a 3-min perfusion with 0.11 and 1.1mM of R(+)-pulegone, respectively. In addition, the intracellular Ca(2+) transient was decreased (72.9%) by 3.2mM R(+)-pulegone, with no significant changes in Ca(2+) transient decay kinetics. Moreover, R(+)-pulegone at 1.1mM prolonged the action potential duration at 10, 50, and 90% of repolarisation. The lengthening of the action potential duration may be attributed to the substantial blockade of the outward K(+) currents caused by 1.1mM of R(+)-pulegone (90.5% at 60 mV). These findings suggest that R(+)-pulegone exerts its negative inotropic effect on mammalian heart mainly by decreasing the L-type Ca(2+) current and the global intracellular Ca(2+) transient.
本研究旨在探究（+）-胡薄荷酮对哺乳动物心脏的变力效应，（+）-胡薄荷酮是薄荷属植物中发现的一种单萜。在电刺激豚鼠心房中，（+）-胡薄荷酮降低收缩力（~83%），并将最大力幅度的 50%时的收缩时间（CT（50））从 45.8 ± 6.2ms 缩短至 36.9 ± 6.2ms，表明（+）-胡薄荷酮可能对钙稳态有影响。硝苯地平（40 μM）作为阳性对照，表现出非常相似的作用模式。为了探究（+）-胡薄荷酮可能影响钙处理的假说，我们测定了 CaCl2 和 BAY K8644 的浓度-反应曲线。（+）-胡薄荷酮使这些曲线向右移位。使用分离的小鼠心室肌细胞，我们测量了全细胞 L 型钙电流，并观察到 0.11 和 1.1mM 的（+）-胡薄荷酮灌流 3 分钟后，I（Ca，L）峰值分别降低了 13.7 ± 2.5%和 40.2 ± 2.9%。此外，3.2mM 的（+）-胡薄荷酮使细胞内钙瞬变降低（72.9%），而[Ca2+]i 瞬变衰减动力学无明显变化。此外，1.1mM 的（+）-胡薄荷酮延长了动作电位时程在复极化 10%、50%和 90%时的时程。动作电位时程的延长可能归因于 1.1mM 的（+）-胡薄荷酮对外向 K+电流的显著抑制（60mV 时为 90.5%）。这些发现表明，（+）-胡薄荷酮对哺乳动物心脏的负性变力作用主要是通过降低 L 型钙电流和整体细胞内钙瞬变来实现的。
