Tissue levels of several radiolabelled beta-adrenoceptor antagonists after intravenous administration in rats

The uptake of radioactively labelled propranolol, oxprenolol, metoprolol, acebutolol, practolol and atenolol into brain, liver and lung tissue was studied five min after intravenous administration (1.0 mg/kg) in normotensive Wistar rats anaesthetised with nitrous oxide and halothane. All of the beta-adrenoceptor antagonists including the least lipophilic compounds atenolol and practolol were detected in brain tissue five min after systemic administration. However, the level of propranolol (as measured by total radioactivity) in the bran was 40 and 67 times greater than the levels found for atenolol and practolol, respectively. Additionally, 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. Levels of radioactivity 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 anaesthetised rats and a tendency towards high tissue levels of radioactivity was found in the animals which received the beta-adrenoceptor antagonists under anaesthesia. Pretreatment of groups of rats for 7, 14 and 21 days with unlabelled atenolol (1.0 mg/kg/day, i.p.) caused an increase in the subsequent central uptake of labelled atenolol whilst both the blood levels of radioactivity and the uptake into peripheral tissues were significantly lower in the 2 and 3 week pretreated rats compared to the control animals. These results are consistent with the hypothesis that a central action may contribute to the antihypertensive effect of beta-adrenoceptor antagonists.