Cardiovascular effects of chronic ifenprodil in a model of central sympathetic stimulation.
In the present study we investigated the effects of a long-term treatment (14 days) with ifenprodil on the excitatory haemodynamic responses induced by central pharmacological stimulation in anaesthetised rabbits. The intracerebroventricular injection of L-glutamate (3 mg/kg) induced important rises in dP/dtmax (32.9%), mean arterial pressure (42.6%) and in the myocardial oxygen consumption index: the triple product (84.2%). Ifenprodil (1.5, 3 and 6 mg/kg/day, i.p.) reduced the increases in myocardial oxygen demand induced by intracerebral L-glutamate in a dose-related manner. Interestingly, ifenprodil also reduced in a dose-dependent manner the maximum values of the oxygen demand indices reached during the central nervous system stimulation. These results indicate that the long-term treatment with ifenprodil can reduce the myocardial oxygen consumption induced by central nervous system stimulation without significant depression of the resting cardiac function. This favourable effect of ifenprodil is in fact a consequence of the association of mild inhibitory effects on the three parameters taken into account in the triple product index of myocardial oxygen consumption.
Catelli
M
M
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, Brazil.
Monassier
L
L
Feldman
J
J
Tibiriçá
E
E
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D018698:Glutamic Acid / Q000008:administration & dosage; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006439:Hemodynamics / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D018698:Glutamic Acid; C010739:ifenprodil; D010100:Oxygen