Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis.
Comparative inotropic effect of calcium, endothelin-1, and forskolin on ferret papillary muscles during acidosis.
复制标题
酸中毒期间钙、内皮素-1 和毛喉素对雪貂乳头肌的比较正性肌力作用。
DOI：
10.1111/j.1472-8206.1997.tb00188.x
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发表时间：
1997
影响因子：
2.9
通讯作者：
Morgan,JP
中科院分区：
文献类型：
--
作者：
Ishiguro,Y;Morgan,JP
酸中毒影响心肌兴奋-收缩偶联途径中的多个步骤，导致肌原纤维钙敏感性降低和肌浆网功能改变。我们的目的是评估三种不同类型的正性肌力药物在酸中毒条件下的有效性：1）毛喉素，一种增强细胞环AMP浓度的腺苷酸环化酶激活剂，2）升高的细胞外Ca 2+和3）内皮素-1，一种三磷酸肌醇，二酰甘油途径的激活剂。将雪貂乳头肌固定在含有正常生理溶液（pH = 7.4）的器官浴中。测量基线张力后，将肌肉浸泡在酸性溶液（pH = 6.98）中，使张力降低至对照组的40%;随后，用正常生理溶液洗涤肌肉，直到它们恢复至基线。将每种正性肌力剂以足以使张力增加超过基线40%的浓度添加到浴溶液中。然后在持续存在该浓度的变力剂的情况下使溶液酸化（pH = 6.98），并测量所得稳态产生的张力。在正常pH值下，每种正性肌力药物引起的张力增加被调整为相似;相反，在酸中毒中对每种药物的反应显著不同。在酸中毒条件下，内皮素-1是恢复降低的发达张力的最有效的正性肌力药物。这可能是由于肌丝对Ca ~（2+）的敏感性增强，比通过升高细胞外Ca ~（2+）或加入forskolin增加[Ca ~（2+）] i而使肌丝对Ca ~（2+）不敏感更有效。
Acidosis affects multiple steps in the excitation‐contraction coupling pathway of myocardium, producing decreased calcium sensitivity of myofibrils and modification of the function of the sarcoplasmic reticulum. Our aim was to evaluate the effectiveness of three different classes of inotropic agents under acidotic conditions: 1) forskolin, an adenylate cyclase activator that enhances cellular cyclic AMP concentrations, 2) elevated extracellular Ca2+and 3) endothelin‐1, an activator of the inositol triphosphate, diacylglycerol pathway. Ferret papillary muscles were mounted in organ baths containing normal physiological solution (pH = 7.4). After baseline tension was measured, the muscles were bathed in an acidotic solution (pH = 6.98) that decreased tension to 40% of the control; subsequently, the muscles were washed with normal physiological solution until they returned to baseline. Each inotropic agent was added to the bathing solution in a concentration sufficient to increase tension by 40% above the baseline. Then the solution was made acidotic (pH = 6.98) in the continuous presence of that concentration of inotropic agent and the resultant steady‐state developed tension measured. The increases in tension induced by each inotropic agent at normal pH were adjusted to be similar; in contrast, the response to each drug in acidosis was significantly different. Under acidotic conditions, endothelin‐1 was the most effective inotropic agent in restoring the depressed developed tension. This was possibly due to enhancement of the myofilament sensitivity to Ca2+, which was more effective than increasing [Ca2+]ithrough elevating extracellular Ca2+or the addition of forskolin which increased [Ca2+]ibut desensitized the myofilaments to Ca2+.