TISSUE-LEVELS OF SEVERAL RADIOLABELED BETA-ADRENOCEPTOR ANTAGONISTS AFTER INTRAVENOUS ADMINISTRATION IN RATS

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 237  (2) , 180-190
Abstract
The uptake of radioactively labeled propranolol, oxprenolol, metoprolol, acebutotol, practolol and atenolol into brain, liver and lung tissue was studied 5 min after i.v. administration (1.0 mg/kg) in normotensive Wistar rats anesthetized with N2O and halothane. The .beta.-adrenoceptor antagonists including the least lipophilic compounds atenolol and practolol were detected in brain tissue 5 min after systemic administration. The level of propranolol (as measured by total radioactivity) in the brain was 40 and 67 .times. greater than the levels found for atenolol and practolol, respectively. Significantly more radioactivity was detected in lung tissue compared to that in liver tissue for the lipophilic, non-selective .beta.-adrenoceptor antagonists propranolol and oxprenolol. Radioactivity levels in blood, brain, liver and lung were measured 5, 15, 30 and 60 min after administration of either propranolol or atenolol (1.0 mg/kg, i.v.) to both conscious and anesthetized rats and a tendency towards higher tissue levels of radioactivity was found in the animals which received the .beta.-adrenoceptor antagonists under anesthesia. Pretreatment of groups of rats for 7, 14 and 21 days with unlabeled atenolol (1.0 mg/kg per day, i.p.) caused an increase in the subsequent central uptake of labeled atenolol while the blood levels of radioactivity and the uptake into peripheral tissues were significantly lower in the 2 and 3 wk pretreated rats compared to the control animals. A central action may contribute to the antihypertensive effect of .beta.-adrenoceptor antagonists.