Kaygisiz Ziya, Ozden H, Erkasap N, Koken T, Gunduz T, Ikizler M, Kural T
Eskisehir Osmangazi University Department of Physiology, Medical Faculty 26480 Eskisehir Turkey.
Acta Physiol Hung. 2010 Dec;97(4):362-74. doi: 10.1556/APhysiol.97.2010.4.2.
Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.
尽管有一些研究涉及胰岛淀粉样多肽对心脏的影响，但胰岛淀粉样多肽诱导正性肌力作用的机制尚不清楚。因此，我们研究了胰岛淀粉样多肽诱导正性肌力作用潜在的信号通路，并比较了大鼠胰岛淀粉样多肽（rAmylin）和人胰岛淀粉样多肽（hAmylin）对心脏的影响。
在恒流条件下灌注离体大鼠心脏，并向心脏中注入rAmylin或hAmylin。测量冠状动脉灌注压、心率、左心室舒张末压以及左心室压力最大上升速率（+dP/dtmax）和左心室压力最大下降速率（-dP/dtmin）。
浓度为1、10或100 nM的rAmylin显著降低冠状动脉灌注压，但增加心率、左心室舒张末压、+dP/dtmax和 -dP/dtmin。注入蛋白激酶A（PKA）抑制剂H-89（50 μM）并未改变rAmylin（100 nM）诱导的正性肌力作用。L型Ca2+通道阻滞剂地尔硫卓（1 μM）和肌浆网（SR）Ca2+释放通道开放剂ryanodine（10 nM）均完全抑制rAmylin诱导的正性肌力作用，但强效蛋白激酶C（PKC）抑制剂星形孢菌素（100 nM）仅部分抑制该作用。hAmylin（1、10和100 nM）对冠状动脉灌注压、心率、舒张末压、+dP/dtmax和 -dP/dtmin均无显著影响。
我们得出结论，rAmylin可能对大鼠心脏产生血管舒张、正性变时和正性肌力作用。通过L型Ca2+通道的Ca2+内流、PKC的激活以及通过ryanodine敏感的Ca2+通道从SR释放Ca2+可能参与了这种正性肌力作用。hAmylin可能对离体灌注大鼠心脏的灌注压、心率和收缩性无显著影响。
