Atenolol and Beta-Adrenergic Blockade: A Kinetic-Dynamic Study in Rats

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Abstract

The objective of our study was to analize the pharmacokinetics, central and peripheral profile, of atenolol (3mg/kg-1,EV) in vagotomized sham oper-ated rats (SO) and in vagotomized aortic coarctatedrats (ACo). Wistar vagotomized and anesthetizedrats were used (250-350 g) either SO or ACo. A microdialysis shunt probe was inserted in the carotid artery and atenolol was measured in dialysate samples by HPLC-fluorometry. A concentric microdialysis probe was inserted in the posterior hypothalamus. Changes of blood pressure and heart rate were measured in both groups. The analysis of the arterial dialy sates showed that atenolol distributes following a two-compartment kinetic model. A reduction of heart rate (15%) was seen. We also found a fall of blood pressure (25.3 ± 5.8 mm Hg, n = 6, p <0.05) due to intra-hypothalamic perfusion of atenolol (2 gg/ml) in ACo rats but not in the SO group. In conclusion, atenolol is a beta-blocker that exertsits action peripherally, but which is able to reach the central nervous system. The effect of its intrahypothalamic perfusion may reflect central adrenergic involvement in ACo rats.