Vittone L, Cingolani H E, Mattiazzi R A
J Mol Cell Cardiol. 1985 Mar;17(3):255-63. doi: 10.1016/s0022-2828(85)80008-0.
In isolated rat hearts perfused at constant coronary flow and heart rate the amount of shortening in their major axis (L), the developed tension (T) and their time derivatives (L and T) were measured after different interventions. Relative changes of maximal velocities of contraction (+L, +T) and relaxation (-L, -T) were assessed by the ratio between both velocities (+L/-L, +T/-T). After the interventions, cAMP intracellular levels and cAMP dependent protein kinase activity were measured. The negative inotropic effect of verapamil (10(-7) M) and nifedipine (5 X 10(-7) M) was accompanied by a relatively greater decrease in maximal velocity of relaxation. Consequently the ratio +L/-L increased. Verapamil increased +L/-L from 1.27 +/- 0.07 to 1.57 +/- 0.08 (P less than 0.001). Nifedipine increased +L/-L from 1.25 +/- 0.05 to 1.77 +/- 0.12 (P less than 0.001). Whereas nifedipine increased intracellular cAMP levels from 0.403 +/- 0.036 pmol/mg wet weight to 0.534 +/- 0.047 (P less than 0.05), verapamil did not alter them. Neither verapamil nor nifedipine affected cAMP protein kinase activity. Increasing Ca2+ in the perfusate did not change the ratio +L/-L. A decrease in extracellular Ca2+, on the other hand, produced a greater decrease in -L than in +L, so that the ratio +L/-L increased from 1.27 +/- 0.05 to 1.49 +/- 0.10 (P less than 0.05). No changes were detected in cAMP levels or its protein kinase activity. Similar results were obtained when +T/-T was analyzed. To offset the negative inotropic effect caused by calcium antagonists, either increased extracellular Ca2+ or isoproterenol can be used.(ABSTRACT TRUNCATED AT 250 WORDS)
在以恒定冠状动脉流量和心率灌注的离体大鼠心脏中，在不同干预措施后测量其长轴缩短量（L）、舒张期张力（T）及其时间导数（L和T）。通过收缩（+L，+T）和舒张（-L，-T）的最大速度之比评估收缩和舒张最大速度的相对变化（+L/-L，+T/-T）。干预后，测量细胞内cAMP水平和cAMP依赖性蛋白激酶活性。维拉帕米（10⁻⁷M）和硝苯地平（5×10⁻⁷M）的负性肌力作用伴随着舒张最大速度相对更大的降低。因此，+L/-L比值增加。维拉帕米使+L/-L从1.27±0.07增加到1.57±0.08（P<0.001）。硝苯地平使+L/-L从1.25±0.05增加到1.77±0.12（P<0.001）。硝苯地平使细胞内cAMP水平从0.403±0.036 pmol/mg湿重增加到0.534±0.047（P<0.05），而维拉帕米未改变其水平。维拉帕米和硝苯地平均不影响cAMP蛋白激酶活性。灌注液中Ca²⁺增加不会改变+L/-L比值。另一方面，细胞外Ca²⁺减少导致-L的降低比+L更大，因此+L/-L比值从1.27±0.05增加到1.49±0.10（P<0.05）。cAMP水平或其蛋白激酶活性未检测到变化。分析+T/-T时也得到了类似结果。为抵消钙拮抗剂引起的负性肌力作用，可使用增加细胞外Ca²⁺或异丙肾上腺素的方法。（摘要截断于250字）
