PMID- 9388044
OWN - NLM
STAT- MEDLINE
DCOM- 19980210
LR  - 20190724
IS  - 0160-2446 (Print)
IS  - 0160-2446 (Linking)
VI  - 30
IP  - 5
DP  - 1997 Nov
TI  - Effects of long-term treatment with the calcium antagonist AE0047 on 
      cerebrovascular autoregulation and hypertrophy in spontaneously hypertensive 
      rats.
PG  - 616-22
AB  - Chronic hypertension is associated with structural and functional changes in the 
      cerebrovascular bed, which influence cerebral circulation and its autoregulation. 
      We examined whether or not long-term treatment of spontaneously hypertensive rats 
      (SHRs) with the new calcium antagonist AE0047 would reverse structural changes in 
      the cerebral vasculature and normalize the elevated lower blood pressure (BP) 
      limit of the cerebral blood flow (CBF) autoregulation. Treating 6-month-old SHRs 
      with a diet containing either 0.013 or 0.04% AE0047 for 8 weeks reduced BP and, 
      at the higher dose, maintained BP at a level similar to that of age-matched 
      Wistar-Kyoto (WKY) rats. At the end of the treatment period, CBF was measured by 
      using the hydrogen-clearance method, and the lower limit of the autoregulation 
      curve was estimated by repeated CBF measurement with stepwise reduction of BP 
      through bleeding. This limit was significantly higher in untreated SHRs than in 
      WKY rats (111 +/- 8 vs. 60 +/- 8 mm Hg). AE0047 caused a significant and 
      dose-dependent shift in the elevated lower BP limit, which decreased to 83 +/- 9 
      and 75 +/- 6 mm Hg at the low and high dose, respectively. In perfusion-fixed 
      proximal, intermediate, and distal portions of the middle cerebral artery, media 
      thickness/external diameter (M/ED) ratios were significantly greater in untreated 
      SHRs than in WKY rats. In AE0047-treated animals, M/ED ratios in all portions 
      tended to be reduced halfway between those for untreated SHRs and those for WKY 
      rats, but with no statistical significance. These results suggest that long-term 
      treatment of patients with hypertension with AE0047 will normalize the 
      autoregulatory threshold while preserving CBF and thereby improve tolerance to BP 
      reduction, but the potential to ameliorate structural alterations may be small.
FAU - Shinyama, H
AU  - Shinyama H
AD  - Pharmacology Laboratories, Research Division, The Green Cross Corporation, 
      Hirakata, Osaka, Japan.
FAU - Nagai, H
AU  - Nagai H
FAU - Kawamura, T
AU  - Kawamura T
FAU - Narita, Y
AU  - Narita Y
FAU - Nakamura, N
AU  - Nakamura N
FAU - Kagitani, Y
AU  - Kagitani Y
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cardiovasc Pharmacol
JT  - Journal of cardiovascular pharmacology
JID - 7902492
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 116308-55-5 (AE0047)
SB  - IM
MH  - Animals
MH  - Blood Pressure/*drug effects
MH  - Calcium Channel Blockers/administration & dosage/*pharmacology/therapeutic use
MH  - Cerebral Arteries/drug effects/pathology
MH  - Cerebrovascular Circulation/*drug effects
MH  - Dihydropyridines/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Homeostasis/drug effects
MH  - Hypertension/*drug therapy/pathology
MH  - Hypertrophy
MH  - Male
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
EDAT- 1997/12/05 00:00
MHDA- 1997/12/05 00:01
CRDT- 1997/12/05 00:00
PHST- 1997/12/05 00:00 [pubmed]
PHST- 1997/12/05 00:01 [medline]
PHST- 1997/12/05 00:00 [entrez]
AID - 10.1097/00005344-199711000-00012 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol. 1997 Nov;30(5):616-22. doi: 
      10.1097/00005344-199711000-00012.