Protective effects of centrally acting sympathomodulatory drugs on myocardial ischemia induced by sympathetic overactivity in rabbits.
It is recognized that an imbalance of the autonomic nervous system is involved in the genesis of ventricular arrhythmia and sudden death during myocardial ischemia. In the present study we investigated the effects of clonidine and rilmenidine, two centrally acting sympathomodulatory drugs, on an experimental model of centrally induced sympathetic hyperactivity in pentobarbital-anesthetized New Zealand albino rabbits of either sex (2-3 kg, N = 89). We also compared the effects of clonidine and rilmenidine with those of propranolol, a beta-blocker, known to induce protective cardiovascular effects in patients with ischemic heart disease. Central sympathetic stimulation was achieved by intracerebroventricular injection of the excitatory amino acid L-glutamate (10 micro mol), associated with inhibition of nitric oxide synthesis with L-NAME (40 mg/kg, iv). Glutamate triggered ventricular arrhythmia and persistent ST-segment shifts in the ECG, indicating myocardial ischemia. The intracisternal administration of clonidine (1 microg/kg) and rilmenidine (30 microg/kg) or of a nonhypotensive dose of rilmenidine (3 microg/kg) decreased the incidence of myocardial ischemia (25, 14 and 25%, respectively, versus 60% in controls) and reduced the mortality rate from 40% to 0.0, 0.0 and 12%, respectively. The total number of ventricular premature beats per minute fell from 30 +/- 9 in the control group to 7 +/- 3, 6 +/- 3 and 2 +/- 2, respectively. Intravenous administration of clonidine (10 micro g/kg), rilmenidine (300 microg/kg) or propranolol (500 microg/kg) elicited similar protective effects. We conclude that clonidine and rilmenidine present cardioprotective effects of central origin, which can be reproduced by propranolol, a lipophilic beta-blocking agent.
Catelli
M
M
Departamento de Fisiologia e Farmacodinâmica, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brasil.
Feldman
J
J
Bousquet
P
P
Tibirica
E
E
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology*; D011817:Rabbits; D000077769:Rilmenidine; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D010080:Oxazoles; D018698:Glutamic Acid; D011433:Propranolol; D003000:Clonidine; D000077769:Rilmenidine; D019331:NG-Nitroarginine Methyl Ester