Cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat.

D- and L-baclofen were given intrathecally at the T2 spinal level in the anaesthetized rat. D-Baclofen, in doses of 7, 35 and 70 nmol produced graded increases in arterial pressure but heart rate remained unaffected. Responses appeared within 30 s, peaked at 2 min and decayed over the next 5 min. Injection i.v. of 70 nmol of D-baclofen failed to alter arterial pressure or heart rate. In contrast, intrathecal administration of L-baclofen decreased both arterial pressure and heart rate. The amplitude and time course of the effects depended on the dose used; 700 nmol of L-baclofen had stronger and longer effects than those induced by 70 nmol, while 7 nmol had no effect. (I.v. injection of 70 nmol of L-baclofen had similar effects to intrathecal administration but with different time course and amplitude.) When given at the T9 level at doses of 70 nmol, D- and L-baclofen had effects similar to those observed at the second thoracic level. Effects of intrathecal administration of D- and L-baclofen at T2 were prevented by pretreatment with either hexamethonium (10 mg/kg i.v.) or lidocaine (25 microliters of a 1% solution, intrathecally). The results suggest that D- and L-baclofen-sensitive receptors in the spinal cord are involved in regulating sympathetic output in pathways to the vessels and/or to the heart. In addition, our results suggest that D- or L-baclofen may not act via classical GABAB receptors or that two types of GABAB receptor exist in spinal sympathetic pathways.