The cerebrovascular effects of curare and histamine in the rat

The effects of histamine and curare on cerebral blood flow (CBF) were measured in rats with an intact blood-brain barrier (BBB) and in rats in which the BBB was disrupted by hypertonic urea. Using radioactive microspheres cortical and subcortical CBF were measured in paralyzed ventilated rats anesthetized with 70% N₂O, 30% oxygen. Blood gas tensions were controlled by mechanical ventilation. In rats with an intact BBB, neither histamine infusion (10 μg·kg^-1·min^-1) nor curare (1 and 5 mg/kg) increased CBF. Twenty minutes after the BBB was disrupted by 2 M urea, histamine (10 μg·kg^-1·min^-1) produced an increase in cortical (180-210 ml·100g^-1·min^-1) and subcortical CBF (103 to 124 ml·10g^-1·min^-1). Twenty minutes after BBB disruption, curare also produced a significant increase in cortical CBF (1 mg/kg: 176-201 ml·100g^-1·min^-1, 5 mg/kg: 190-209 ml·100g^-1·min^-1). The increases in CBF produced by curare were completely blocked by pretreatment with 30 mg/kg cimetidine, a histamine H₂ receptor antagonist, 3 min before curare. The results indicate that curare may produce cerebrovasodilation and increases in CBF by release of histamine and stimulation of central nervous system H₂ receptors. These effects occur only when the BBB is disrupted and circulating histamine has access to brain perivascular tissue.