Williamson A P, Seifen E, Lindemann J P, Kennedy R H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock 72205.
Am J Physiol. 1994 Jun;266(6 Pt 2):H2462-7. doi: 10.1152/ajpheart.1994.266.6.H2462.
This study was designed to determine the role of the alpha 1-adrenergic receptor (AR) subtypes in the positive inotropic action of alpha 1-adrenergic agonists in rat myocardium. Isolated left atrial and papillary muscle were suspended in oxygenated Krebs-Henseleit buffer (37 degrees C) containing 3 microM nadolol and paced at 3.3 Hz. Isometric tension was continuously monitored. Cumulative concentration-response curves for phenylephrine (3 x 10(-7) to 3 x 10(-4) M) were obtained in the presence and absence of WB4101 (4 and 10 nM) and with and without treatment with chloroethylclonidine (CEC; 10, 100, and 300 microM). WB4101 antagonized the effect of phenylephrine in both tissues, increasing half-maximal effective concentration (EC50) values in a concentration-dependent manner. CEC pretreatment also increased EC50 values in both tissues, and 300 microM CEC reduced the maximal positive inotropic effect of phenylephrine by approximately 48 and 38% in left atrial and papillary muscle, respectively. CEC alone elicited significant increases in contractile force that were not readily reversible. These data suggest that the positive inotropic effect of alpha 1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of both WB4101- and CEC-sensitive alpha 1-ARs.
本研究旨在确定α1 - 肾上腺素能受体（AR）亚型在α1 - 肾上腺素能激动剂对大鼠心肌正性肌力作用中的作用。将离体左心房和乳头肌悬于含3μM纳多洛尔的氧合Krebs - Henseleit缓冲液（37℃）中，以3.3 Hz的频率起搏。连续监测等长张力。在有和无WB4101（4和10 nM）以及有和无氯乙可乐定（CEC；10、100和300μM）处理的情况下，获得去氧肾上腺素（3×10⁻⁷至3×10⁻⁴ M）的累积浓度 - 反应曲线。WB4101拮抗了去氧肾上腺素在两种组织中的作用，以浓度依赖性方式增加了半数最大有效浓度（EC50）值。CEC预处理也增加了两种组织中的EC50值，并且300μM CEC分别使左心房和乳头肌中去氧肾上腺素的最大正性肌力作用降低了约48%和38%。单独使用CEC可引起收缩力显著增加，且不易逆转。这些数据表明，α1 - 肾上腺素能激动剂在大鼠心房和心室心肌中的正性肌力作用是由对WB4101和CEC敏感的α1 - ARs的刺激所致。
