Baclofen prevents the increase of myocardial oxygen demand indexes evoked by the hypothalamic stimulation in rabbits.
The electrical stimulation of the paraventricular nucleus (PVN) of the hypothalamus in anaesthetized rabbits elicited important cardiovascular responses which were mainly characterized by increases in arterial pressure, dP/dtmax, and of the indexes of myocardial oxygen consumption, rate-pressure product (from 34 +/- 2 to 40 +/- 2 mmHg.bpm.10(-3) and triple product (from 102 +/- 12 to 162 +/- 19 mmHg2.s-1.bpm.10(-6). The hemodynamic alterations induced by PVN stimulation were similar to those observed during physical effort and stressful situations. Intracerebroventricular (0.1, 0.3 and 1 microgram.kg-1) or intravenous administration (1, 3 and 10 mg.kg-1) of baclofen, a selective GABAB receptor agonist, induced a dose-related decrease in the peak values of dP/dtmax and of the indexes of myocardial oxygen consumption (rate-pressure and triple products) during the electrical PVN stimulation. After 1 microgram.kg-1 baclofen (i.c.v.), the peak value of the triple product during PVN stimulation was 101 +/- 21 as compared to 149 +/- 15 before treatment. At the 10 mg.kg-1 dose (i.v.), the triple product during stimulation only reached 90 +/- 20 vs. 150 +/- 20 before treatment. These results suggested that a type B GABAergic transmission system is involved in the modulation of central control of the cardiac function. Drugs modulating this system could therefore be designed to blunt the myocardial oxygen demand increases.
Tibirica
E
E
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS URA 589, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Monassier
L
L
Feldman
J
J
Brandt
C
C
Verdun
A
A
Bousquet
P
P
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology*; D011817:Rabbits; D018079:Receptors, GABA / Q000378:metabolism
D005971:Glutamates; D018079:Receptors, GABA; D018698:Glutamic Acid; D001418:Baclofen; D007608:Kainic Acid