Evidence for a spinal origin of the effect of baclofen on the myocardial oxygen demand indexes.
In a previous study in anaesthetized rabbits we observed that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) elicited substantial rises in the maximum rate of change of left ventricular pressure (dP/dtmax) and in myocardial oxygen demand indexes (rate-pressure product and triple product), similar to the changes observed during stress or physical effort. Baclofen, a selective GABA(B) receptor agonist, injected intravenously prevented these responses. In the present study, we show that low doses of baclofen (0.1, 0.3 and 1 microgram/kg), injected intrathecally (i.t.) at the T9 level, reduced the myocardial oxygen demand during PVN stimulation. After 0.3 microgram/kg baclofen i.t., the peak value of the triple product during stimulation was 140 +/- 20 compared with 193 +/- 20 before treatment. An i.t. injection (500 micrograms/kg), of saclofen a selective GABA(B) receptor antagonist, did not modify the resting haemodynamics significantly but attenuated the inhibitory effects of baclofen (3 mg/kg i.v.). These results suggest that the main site of the effects of baclofen is located within the spinal cord and that GABA(B) receptors probably mediate these effects by modulating the central control of cardiac function. In conclusion, baclofen might be a useful tool to prevent the centrally evoked increases of myocardial oxygen demand.
Monassier
L
L
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS URA 589, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Tibiriça
E
E
Roegel
J C
JC
Feldman
J
J
Bousquet
P
P
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology*; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D011817:Rabbits; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
D018755:GABA Agonists; D018756:GABA Antagonists; D058788:GABA-B Receptor Antagonists; D001418:Baclofen; C080629:saclofen; D010100:Oxygen