CARDIOVASCULAR EFFECTS OF INTRACEREBROVENTRICULAR d-, l- AND dl-PROPRANOLOL IN THE CONSCIOUS RABBIT

¹ Department of Clinical Pharmacology and M.R.C. Clinical Pharmacology Research Group, Royal Postgraduate Medical School, London, United Kingdom

The possibility that the antihypertensive effect of propranolol may in part be mediated centrally has been investigated by intracerebroventricular (ICV) injection of the drug in the conscious rabbit. Single injections of 500 µg of dl-propranolol to each rabbit produced an initial rise in mean arterial pressure (MAP) of 27.5 ± 6.0 mm Hg at 5 minutes followed by a prolonged fall (8.9 ± 3.3 mm Hg at 4 hours). Central administration of l-propranolol (500 µg) also caused the early increase in MAP (20.7 ± 4.1 mm Hg at 5 minutes) but the subsequent fall was greater (14.6 ± 4.5 mm Hg at 4 hours). The MAP did not change after l-propranolol (500 µg) was injected intravenously. ICV d-propranolol (500 µg), which is virtually devoid of beta adrenoceptor blocking activity, produced the early rise in MAP (42.5 ± 4.4 mm Hg at 5 minutes) but did not cause the late fall. The increase in MAP appears to be a result of the local anesthetic activity possessed by both isomers. This was confirmed by the recording of a similar rise (51.0 ± 10.0 mm Hg at 5 minutes) after ICV injection of procaine (1 mg). Pentobarbital sodium anesthesia abolished the early pressor response to both procaine and d-propranolol. ICV l-propranolol blocked the normal transient fall in MAP and tachycardia produced by centrally administered isoproterenol, indicating the presence of central adrenoceptor blockade. It is proposed that propranolol can lower blood pressure by an action within the central nervous system.

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