Spinal mediation of the increases in arterial pressure and heart rate in response to intrathecal administration of bicuculline

The present experiments were designed to determine the mechanisms by which the intrathecal administration of the GABAA antagonist, bicuculline (2.2 and 8.8 nmol), at the second thoracic spinal segment (T2) affects cardiovascular function in the anaesthetized rat. Bicuculline produced a dose-related, transient increase in arterial pressure and heart rate which peaked at 5-7 min and persisted for 30 min or more, depending on dose. There was a mutually reversible interaction between bicuculline and intrathecal administration of the GABAA agonist, muscimol (8.8 nmol), which alone decreased arterial pressure and heart rate. Bicuculline was given intrathecally at the third lumbar spinal level (8.8 nmol) and intravenously (8.8 nmol), but in these cases it failed to affect these cardiovascular parameters. Pretreatment with intrathecal infusion of 15 microliters of 1% lidocaine or with intravenous injection of hexemathonium (10 mg/kg) prevented the responses to intrathecal administration of 8.8 nmol of bicuculline at T2. These results demonstrate that the effects of bicuculline on arterial pressure and heart rate are due to an action in the spinal cord on GABAA receptors, and the data may be interpreted as indicating that there is a tonic GABAergic inhibition of sympathetic outflow at the spinal level.