Changes in rat hind limb vascular resistance following intracerebroventricular drug administration

The right hind limbs of rats (which had previously implanted intraventricular guide cannulae) were isolated from the systemic circulation, but with the nerves to the limb remaining intact, and perfused using a constant output blood pump. Using this preparation, changes in vascular resistance, blood pressure and heart rate were monitored following injection of noradrenaline, phentolamine and propranolol into the lateral cerebral ventricles (i.c.v.) of rats anaesthetised with alpha-chloralose. All three drugs lowered blood pressure. Noradrenaline administered i.c.v. induced a nervously mediated vasocilatation and an insignificant fall in heart rate whereas i.c.v. phentolamine administration was followed by a nervously mediated vasoconstriction in the isolated hind limb and a gradual rise in heart rate. After i.c.v. administration of propranolol there was no evidence of an immediate nervously mediated vasodilatation but heart rate fell significantly. Following i.c.v. phentolamine or propranolol vasodilatation did not occur in the hind limb until after the time taken for circulating blood ro reach the isolated vascular bed. The vasodilatatory and hypotensive responses to i.c.v. noradrenaline were not evident following prior i.c.v. injection of phentolamine. These results indicate the suitability of this preparation for investigations of central actions of other drugs.