Mechanism of the tachycardia following systemic alpha-methyldopa administration in conscious rats.
The mechanism of the tachycardia observed in conscious rats following systemic administration of alpha-methyldopa (alpha-MD) was investigated. Heart rate and mean arterial pressure were monitored following peripheral (i.p. and i.v.) and central (lateral and fourth ventricle and cisterna magna) administration of alpha-MD. As little as 25 mg/kg i.p. produced the maximum tachycardia observed: 136 +/- 30 beats/min within 30 min. However, after central administration of alpha-MD--producing similar reductions in blood pressure--only a gradually developing bradycardia occurred (maximum at 3-4 h), suggesting that the tachycardia was peripheral in origin. Tachycardia following administration of 25 mg/kg alpha-MD i.p. was prevented by pretreatment with propranolol, desmethylimipramine, and the dopa-decarboxylase inhibitor R04-4602, but not by pretreatment with pentolinium, guanethidine, the dopamine-beta-hydroxylase inhibitor FLA-63, or by adrenalectomy or depletion of endogenous catecholamines. In isolated spontaneously beating atria, alpha-MD produced a maximum increase in rate similar to that of isoprenaline. This effect of alpha-MD was blocked by propranolol and R04-4602 but not by FLA-63. These results suggest that the tachycardia observed in conscious rats following alpha-MD administration is caused by stimulation of cardiac beta-adrenoceptors following its conversion to alpha-methyldopamine in cardiac sympathetic neurons.
D000818:Animals; D006339:Heart Rate / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008750:Methyldopa / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D008750:Methyldopa