Williamson A P, Seifen E, Lindemann J P, Kennedy R H
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock.
J Pharmacol Exp Ther. 1994 Mar;268(3):1174-82.
This study was designed to determine if the positive and negative inotropic actions of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium are mediated via different alpha-1-adrenergic receptor (AR) subtypes. Inotropic effects of phenylephrine were examined in isolated left atrial and papillary muscle before and after treatment with prazosin, WB4101 (N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxin+ ++-2-methanamine), chloroethylclonidine (CEC) and WB4101 plus CEC. Phenylephrine (10 microM) elicited a monophasic positive inotropic response in left atrial muscle and a triphasic inotropic action in papillary muscle (transient positive, then negative inotropic components preceding a sustained positive inotropic response). CEC, WB4101 and prazosin each antagonized the monophasic response in isolated left atria and the sustained positive inotropic response in papillary muscle. CEC and prazosin each antagonized the transient negative inotropic component in papillary muscle. The transient positive inotropic response was not affected by CEC, WB4101 or CEC plus WB4101, but was antagonized by higher concentrations of prazosin. These data suggest that the sustained positive inotropic effect of alpha-1-adrenergic agonists in rat atrial and ventricular myocardium results from stimulation of alpha-1A and alpha-1B ARs, whereas the transient negative inotropic component of the triphasic response in ventricular preparations is mediated via alpha-1B ARs. However, present data do not exclude the possibility that the CEC-sensitive inotropic responses elicited by phenylephrine may be mediated in part by other recently described alpha-1 subtypes. The receptors involved in the transient positive inotropic action cannot be identified by current results.
本研究旨在确定α-1肾上腺素能激动剂在大鼠心房和心室心肌中的正性肌力和负性肌力作用是否通过不同的α-1肾上腺素能受体（AR）亚型介导。在用哌唑嗪、WB4101（N-[2-(2,6-二甲氧基苯氧基)乙基]-2,3-二氢-1,4-苯并二恶英-2-甲胺）、氯乙可乐定（CEC）以及WB4101加CEC处理前后，检测了去氧肾上腺素对离体左心房和乳头肌的肌力作用。去氧肾上腺素（10μM）在左心房肌中引发单相正性肌力反应，在乳头肌中引发三相肌力作用（短暂正性，然后在持续正性肌力反应之前出现负性肌力成分）。CEC、WB4101和哌唑嗪均拮抗离体左心房中的单相反应以及乳头肌中的持续正性肌力反应。CEC和哌唑嗪均拮抗乳头肌中的短暂负性肌力成分。短暂正性肌力反应不受CEC、WB4101或CEC加WB4101的影响，但被较高浓度的哌唑嗪拮抗。这些数据表明，α-1肾上腺素能激动剂在大鼠心房和心室心肌中的持续正性肌力作用是由α-1A和α-1B ARs的刺激引起的，而心室制剂中三相反应的短暂负性肌力成分是通过α-1B ARs介导的。然而，目前的数据并不排除去氧肾上腺素引发的CEC敏感的肌力反应可能部分由其他最近描述的α-1亚型介导的可能性。目前的结果无法确定参与短暂正性肌力作用的受体。
