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.
Hong
Y
Y
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Henry
J L
JL
D000772:Anesthesia, Local; D000775:Anesthesia, Spinal; D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005725:Ganglia, Autonomic / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D011978:Receptors, Nicotinic; D001418:Baclofen