PMID- 6500669
OWN - NLM
STAT- MEDLINE
DCOM- 19841231
LR  - 20190722
IS  - 0194-911X (Print)
IS  - 0194-911X (Linking)
VI  - 6
IP  - 5
DP  - 1984 Sep-Oct
TI  - Effect of methyldopa on brain cholinergic neurons involved in cardiovascular 
      regulation. A study in conscious spontaneously hypertensive rats.
PG  - 614-21
AB  - Chemical stimulation of brain cholinergic neurons in many species can produce 
      hypertension. Recent studies in this laboratory have demonstrated that clonidine 
      inhibits this central cholinergic pressor response by inhibiting the biosynthesis 
      of brain acetylcholine. This study was designed to determine whether methyldopa, 
      like clonidine, could inhibit brain cholinergic neurons involved in 
      cardiovascular regulation in freely-moving spontaneously hypertensive rats (SHR). 
      Intravenous (i.v.) injection of methyldopa (50-200 mg/kg) produced a dose-related 
      fall in blood pressure (29/15-54/33 mm Hg) in SHR. Intracerebroventricular 
      (i.c.v.) injection of hemicholinium-3 (HC-3) in SHR evoked a fall in arterial 
      pressure through inhibition of acetylcholine synthesis. Doses of HC-3 (10 
      micrograms, or 15 micrograms, i.c.v.) and methyldopa (50 mg/kg, i.v.) were 
      administered to produce small reductions in arterial pressure in SHR (7-14 mm Hg 
      diastolic, respectively). When the two agents were injected simultaneously, 
      however, a greater than additive response was obtained (p less than 0.05). 
      Central injection of echothiophate (a long-acting cholinesterase inhibitor) to 
      potentiate brain cholinergic activity resulted in a sustained hypertensive 
      response (greater than 40 mm Hg) in SHR for at least 150 minutes. Simultaneous 
      injection of or pretreatment with methyldopa (100 mg/kg, i.v.) inhibited the 
      pressor response to echothiophate over a time course similar to its 
      antihypertensive response in untreated SHR. Methyldopa, however, was completely 
      ineffective in altering the hypertensive response to central injection of 
      carbachol (1 microgram, i.c.v.). This difference in methyldopa susceptibility 
      between the indirect-acting (echothiophate) and direct-acting (carbachol) 
      cholinergic agonists may be related to an inhibiting effect of methyldopa on 
      brain acetylcholine release.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Buccafusco, J J
AU  - Buccafusco JJ
LA  - eng
GR  - HL 30046/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Receptors, Cholinergic)
RN  - 312-45-8 (Hemicholinium 3)
RN  - 56LH93261Y (Methyldopa)
RN  - BA9QH3P00T (Echothiophate Iodide)
RN  - MN3L5RMN02 (Clonidine)
SB  - IM
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Brain/*drug effects
MH  - Clonidine/pharmacology
MH  - Echothiophate Iodide/pharmacology
MH  - Hemicholinium 3/pharmacology
MH  - Male
MH  - Methyldopa/*pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Receptors, Cholinergic/*drug effects
EDAT- 1984/09/01 00:00
MHDA- 1984/09/01 00:01
CRDT- 1984/09/01 00:00
PHST- 1984/09/01 00:00 [pubmed]
PHST- 1984/09/01 00:01 [medline]
PHST- 1984/09/01 00:00 [entrez]
AID - 10.1161/01.hyp.6.5.614 [doi]
PST - ppublish
SO  - Hypertension. 1984 Sep-Oct;6(5):614-21. doi: 10.1161/01.hyp.6.5.614.