Differences in the central hypotensive actions of alpha-methyldopa and clonidine in the spontaneously hypertensive rat: contribution of neurons arising from the B3 and the C1 areas of the rostral ventrolateral medulla.
The rostral ventrolateral medulla (RVLM) is the proposed site of origin of bulbospinal excitatory vasomotor neurons, and this brainstem area gives rise to chemically distinct populations of neurons, including serotonin-containing neurons of the B3 group and epinephrine-containing neurons of the C1 group, which independently serve sympathoexcitatory functions. In the present study, we sought to establish (a) whether distinct and chemically specific pathways originating in the C1 or B3 regions are involved in the antihypertensive effects of alpha-methyldopa (methyldopa) and clonidine and (b) if so, whether these effects are related to an activation of alpha-adrenoceptors in these areas. Microinjections of methyldopa (6 nmol) or clonidine (5 nmol) were made in the C1 or B3 area in intact spontaneously hypertensive rats (SHR), pretreated with 5,7-dihydroxytryptamine (5,7-DHT) or with phentolamine. The microinjection of clonidine into both the B3 and the C1 area caused a rapid decrease in arterial pressure, whereas microinjection of methyldopa lowered the arterial pressure only after injection into the B3 area. Pretreatment with intracerebroventricular (i.c.v.) 5,7-DHT attenuated the hypotension produced by microinjection of clonidine into the B3 area, suggesting that this effect is mediated by serotonin-containing neurons. Central pretreatment with phentolamine reduced the hypotensive effects produced by injection of clonidine into either area and of methyldopa into the B3 region, consistent with previous suggestions that these central effects are mediated through alpha-adrenoceptors. These results suggest that both serotonin-containing and epinephrine-containing neurons contribute to the central action of clonidine, whereas the effects of methyldopa injection in RVLM appear to be mediated by serotonin-containing but not by epinephrine-containing neurons.
Department of Medicine, Flinders University of South Australia, Adelaide.
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G
Drolet
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Aslanian
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J
Minson
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Morris
J
J
Chalmers
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008750:Methyldopa / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D009474:Neurons / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR
D015116:5,7-Dihydroxytryptamine; D008750:Methyldopa; D003000:Clonidine; D010646:Phentolamine