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豚鼠和兔子肺部及心血管系统β受体的差异。

Differences in pulmonary and cardiovascular beta receptors in the guinea pig and rabbit.

作者信息

Weissberg R M, Marian J, Bradshaw J, Alvarez R

出版信息

J Pharmacol Exp Ther. 1977 Aug;202(2):337-45.

PMID:18599
Abstract

An in vivo preparation, in which a body plethysmograph was incorporated, was useful in monitoring the cardiopulmonary effects of pharmacological agents in the guinea pig and rabbit. Isoproterenol, given 30 seconds prior to histamine challenge, reproducibly blocked histamine-induced dynamic compliance decreases and increased heart in the artificially ventilated guinea pig. These effects were used to separate the activity of beta adrenergic blockers on airway and heart muscle. Dose-response data were obtained and ED50 values for pulmonary and cardiovascular blockade were compared. Relative potencies and cardioselectivity ratios for dichloroisoproterenol, practolol, dl-propranolol and d-propranolol were determined. Both practolol and dichloroisoproterenol were cardioselective; dl-propranolol was found to be the most potent. When a similar protocol was tried in the rabbit, isorpoterenol failed to antagonize either histamine or methacholine-induced airway constriction. This finding was supported in subsequent in vitro tests. Isoproterenol and epinephrine were ineffective in blocking methacholine-induced tracheal chain contractions and epinephrine did not significantly enhance adenylate cyclase activity. Our observations suggest rabbit airway smooth muscle is insensitive to beta adrenergic stimulants.

摘要

一种包含体体积描记器的体内制备方法,对于监测豚鼠和兔子体内药物制剂的心肺效应很有用。在组胺激发前30秒给予异丙肾上腺素,可重复性地阻断组胺诱导的人工通气豚鼠动态顺应性降低和心率增加。这些效应被用于区分β肾上腺素能阻滞剂对气道和心肌的活性。获得了剂量反应数据,并比较了肺部和心血管阻断的ED50值。测定了二氯异丙肾上腺素、普拉洛尔、消旋普萘洛尔和右旋普萘洛尔的相对效价和心脏选择性比率。普拉洛尔和二氯异丙肾上腺素均具有心脏选择性;发现消旋普萘洛尔效力最强。当在兔子身上尝试类似方案时,异丙肾上腺素未能拮抗组胺或乙酰甲胆碱诱导的气道收缩。这一发现得到了后续体外试验的支持。异丙肾上腺素和肾上腺素在阻断乙酰甲胆碱诱导的气管链收缩方面无效,且肾上腺素未显著增强腺苷酸环化酶活性。我们的观察结果表明,兔气道平滑肌对β肾上腺素能刺激不敏感。

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