The present study was concerned with the effects on the cardiovascular system of centrally injected beta-blockers. Several lines of approach were used. Intracerebroventricular (icv) injections of dl-propranolol lowered blood pressure and heart rate in halothane (H)-anaesthetised rats, whereas similar injections in thiobutobarbitone (T)-anaesthetised rats only lowered heart rate. The hypotensive effect icv dl-propranolol in H-anaesthetised rats is discussed in terms of a systemic action of the drug following leakage from CSF to the circulation. In H-anaesthetised rats intrahippocampal (i.h.) injections of 1-propranolol (but not d-propranolol) produced dose-related falls in blood pressure and heart rate which were of greater magnitude than those seen after intravenous injection of similar doses. I.h. injection of atenolol and timolol failed to affect blood pressure and heart rate. The hypotensive action of 1-propranolol in the hippocampus appeared to be unrelated to beta-blockade or membrane stabilising activity. In T-anaesthetised rats icv pretreatment with beta-blockers unmasked a pressor response to icv adrenaline. Icv adrenaline alone produced no significant changes in blood pressure. The order of potency of the beta-blockers was ICI 118551 > dl-propranolol > atenolol, suggesting that central beta-blockade necessary for the effect to be expressed. d-Propranolol was ineffective in this respect. Various pharmacological manipulations suggested that the pressor response to adrenaline following icv injection of beta-blockers was due to a central action of the drug, although this was not proved conclusively. In T-anaesthetised rats icv beta-blockers generally failed to modify the pressor responses evoked by electrical stimulation in the anterior hypothalamus, posterior hypothalamus, amygdala and median raphe nucleus. Third ventricle infusions of propranolol in the chloralose anaesthetised cat modified the pressor responses produced by electrical stimulation in the ansa lenticularis. The return of blood pressure to pre-stimulation levels following cessation of stimulation was delayed by centrally, but not intravenously, injected propranolol. This effect appeared to be related to the membrane stabilising properties of the beta-blocker.
|Date of Award||1982|