EFFECT OF ALPHA-ADRENERGIC STIMULATION ON ISOLATED VENTRICULAR MYOCYTES

α-肾上腺素刺激对离体心室肌细胞的影响

• 批准号: 3817601
• 负责人: M C CAPOGROSSI
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3817601
• 关键词: alpha adrenergic agent; calcium metabolism; chemical stimulation; drug interactions; electrostimulus; heart cell; heart contraction; heart pharmacology; heart rhythm; heart ventricle; laboratory rat; membrane permeability; muscle relaxants; muscle stimulant; phenylephrine; propranolol; sarcoplasmic reticulum; single cell analysis

The effect of alpha1-adrenergic stimulation on the inotropy of the myocardium is still controversial. A positive inotropic effect has ben well documented and it is often preceded by a short lived decrease in contractility. Additionally a persistent negative inotropic effect of alpha1 stimulation has also been described in multicellular cardiac preparations. The purpose of this study was to characterized the effect of alpha1 stimulation on the cytosolic Ca2+ (Cai) transient and on the contractile properties of single ventricular myocytes under condition leading either to an enhancement or a decrease in twitch amplitude. Isolated rat ventricular myocytes, pretreated with propranolol were used to investigate the effect of alpha1-adrenergic stimulation with phenylephrine on twitch amplitude (TA) and on the frequency of spontaneous contractile waves (CW), which represent the mechanical expression of spontaneous Ca2+ release from the sarcoplasmic reticulum (SR). In 1 mM bathing (Ca2+) (Cao), during field stimulation at 0.2 Hz, alpha1 had a positive inotropic effect which was reversibly abolished by prazosin and to a considerable extent appeared related to an increased myofilament responsiveness to Ca2+ in addition to some enhancement in the amplitude of the Cai transient associated with the twitch. b. During stimulation at 0.2 hz, in d mM Cao, CW appeared in some of the diastolic intervals. Phenylephrine abolished them and decreased TA. This negative effects was in contrast to the positive action observed in parallel studies in 1 mM Cao. In similar experiments with myocytes loaded with the Ca2+ probe Indo-1 AM the negative effect of alpha1 on TA was associated with a decrease in the amplitude of the Cai transient. c. In the absence of stimulation, in d mM Cao, alpha1 significantly and reversibly reduced CW frequency. This effect could be prevented by the alpha1 blocker prazosin. These findings are consistent with the view that the effect of alpha1-adrenergic stimulation of cardiac cells can vary in relation to intracellular (Ca2+).

α_1肾上腺素能刺激对心肌收缩力的影响 心肌仍然是有争议的。 正性肌力作用具有 ben有很好的文献记载，它通常是在一个短暂的 收缩力下降。 此外，持续的负面影响 α 1刺激的正性肌力作用也已描述于 多细胞心脏制备物。 本研究旨在 为了表征α 1刺激对细胞溶质的影响， Ca 2+（Cai）瞬变和对单个 心室肌细胞在导致 增强或减少抽搐幅度。 分离的大鼠心室肌细胞，用普萘洛尔预处理， 用于研究α 1-肾上腺素能刺激的作用 苯乙哌啶对肌颤幅度（TA）和频率的影响 自发性收缩波（CW），代表 机械表达的自发钙释放从 肌浆网（SR）。 在ImM浴（Ca 2+）（Cao）中，在 0.2Hz的场刺激，α 1具有正性肌力作用 这是可逆地取消了哌唑嗪和一个相当大的 程度似乎与肌丝反应性增加有关 Ca 2+除了在一定程度上增强的幅度， 与抽搐相关的短暂性。 B.在0.2的刺激期间 Hz，在d mM Cao时，CW出现在部分舒张间期。 苯乙醯胺可使上述作用消失，并使TA降低。 这种负面 与平行观察到的积极作用相反， 在ImM Ca 0. 在类似的实验中， 用Ca ~（2+）探针Indo-1 AM检测了α 1对TA的负效应， 与Cai的振幅降低有关 短暂的 C.在没有刺激的情况下，在d mM Cao中，α 1 显著且可逆地降低CW频率。 这种效果 可以通过α 1受体阻滞剂哌唑嗪来预防。 这些发现 与α 1-肾上腺素能的作用 心肌细胞的刺激可以与细胞内的 (Ca2+).