Central and peripheral cardiovascular effects of alpha-methylepinephrine.
We compared peripheral and central cardiovascular effects of (+/-)-alpha-methylepinephrine (alpha-ME) and (+/-)-alpha-methylnorepinephrine (alpha-MNE), two putative active metabolites of alpha-methyldopa to those of (-)-epinephrine in urethane-anesthetized normotensive rats. Intravenous administration of 1 microgram doses of alpha-ME (4.3 nmol) lowered blood pressure whereas alpha-MNE (4.5 nmol) and (-)-epinephrine (3.0 nmol) raised blood pressure. Heart rate responses to each were opposite to the blood pressure response, consistent with reflex buffering. When administered into the cerebral ventricle (5-20 micrograms) (15-90 nmol) and nucleus of the solitary tract (0.3-10 nmol), each catecholamine caused marked reductions in both blood pressure and heart rate. alpha-ME was more potent than alpha-MNE and the endogenous catecholamine, (-)-epinephrine, in its central depressor effect. The greater potency of alpha-ME relative to alpha-MNE and (-)-epinephrine suggests that it could contribute to antihypertensive actions of alpha-methyldopa.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004837:Epinephrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D008771:Nordefrin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
C029205:alpha-methylepinephrine; D008750:Methyldopa; D008771:Nordefrin; D004837:Epinephrine