Chess-Williams R G, Broadley K J
J Cardiovasc Pharmacol. 1984 Jul-Aug;6(4):701-6. doi: 10.1097/00005344-198407000-00024.
Propranolol (3.6 mg kg-1 day-1) was administered to guinea pigs for 14 days via subcutaneously implanted "Alzet" osmotic minipumps. Blockade of cardiac and vascular beta-adrenoceptors was confirmed by a depression of heart rate and blood pressure responses to isoprenaline in anaesthetized animals. After 14 days of propranolol treatment, minipumps were removed and 48 h later beta-adrenoceptor sensitivity was determined in cardiac and lung tissues. Left atrial inotropic responses were unaltered following propranolol withdrawal. However, right atrial chronotropic responses to sympathomimetic amines were supersensitive when compared with tissues from animals implanted with empty minipumps. Relaxation responses of lung strip preparations to beta-adrenoceptor agonists after withdrawal of propranolol were similar to controls. (3H)Dihydroalprenolol binding to ventricular and lung tissue indicated that there was no change in either the dissociation constant (KD) or the maximum number of (3H)DHA binding sites (Bm) in these tissues. These results suggest that following withdrawal from beta-adrenoceptor antagonist treatment there is a selective increase in the chronotropic sensitivity of the heart to sympathomimetic amines.
通过皮下植入的“Alzet”渗透微型泵，以3.6毫克/千克/天的剂量给豚鼠注射普萘洛尔，持续14天。在麻醉动物中，通过心率和血压对异丙肾上腺素反应的降低，证实了心脏和血管β - 肾上腺素能受体的阻断。普萘洛尔治疗14天后，取出微型泵，48小时后测定心脏和肺组织中的β - 肾上腺素能受体敏感性。普萘洛尔撤药后，左心房的变力反应未改变。然而，与植入空微型泵的动物组织相比，右心房对拟交感胺的变时反应超敏。普萘洛尔撤药后，肺条制备物对β - 肾上腺素能激动剂的舒张反应与对照组相似。（3H）二氢阿普洛尔与心室和肺组织的结合表明，这些组织中的解离常数（KD）或（3H）DHA结合位点的最大数量（Bm）均无变化。这些结果表明，从β - 肾上腺素能受体拮抗剂治疗撤药后，心脏对拟交感胺的变时敏感性有选择性增加。
