Differential role of brain ascending noradrenergic bundles in the circulatory effects of alpha-methyldopa and clonidine.
We examined the contribution of the ascending noradrenergic (NA) projections to the circulatory effects of intracisternal (i.c.) administration of clonidine and alpha-methyldopa (alpha-MD) in conscious rabbits. We compared the effects of combined dorsal and ventral NA fibre bundle lesions with those of individual bundle lesions. Local microinjection of 6-hydroxydopamine (6-OHDA) bilaterally into both NA fibre bundles in the midbrain produced marked reduction in norepinephrine (NE) after 4 weeks in all forebrain regions examined, but dopamine concentrations generally were not affected. The decreases in mean arterial pressure (MAP) and heart rate (HR) to i.c. injections of clonidine in animals with forebrain NE depletion were similar to those observed in vehicle-injected animals. In contrast, the normal decrease in HR produced by alpha-MD was abolished in rabbits with lesions of both the dorsal and ventral NA bundle (8% of control) and markedly reduced in rabbits with lesions of only the ventral bundle (33% of control). Lesions of the dorsal bundle alone produced a modest attenuation of bradycardia (62% of control). The effects of the lesions were not observed in sinoaortically denervated (SAD) rabbits, suggesting that the main component of the bradycardia affected was baroreflex vagal facilitation. The effects on the hypotension produced by alpha-MD were only slight.(ABSTRACT TRUNCATED AT 250 WORDS)
Van den Buuse
M
M
Baker Medical Research Institute, Melbourne, Australia.
Head
G A
GA
Korner
P I
PI
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008750:Methyldopa / Q000378:metabolism / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits
D008750:Methyldopa; D016627:Oxidopamine; D003000:Clonidine; D004298:Dopamine; D009638:Norepinephrine