PMID- 9821661
OWN - NLM
STAT- MEDLINE
DCOM- 19990122
LR  - 20190710
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 50
IP  - 10
DP  - 1998 Oct
TI  - Activation of 11 beta-hydroxysteroid dehydrogenase by dehydroepiandrosterone 
      sulphate as an anti-hypertensive agent in spontaneously hypertensive rats.
PG  - 1139-45
AB  - The anti-hypertensive properties of dehydroepiandrosterone sulphate (DHEAS) have 
      been investigated by studying its effects on blood pressure, on serum 
      concentrations of corticosterone and dehydrocorticosterone, and on 11 
      beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity in spontaneously 
      hypertensive rats (SHR). SHR were given intraperitoneal injections of DHEAS (10 
      mg day-1 for 70 days) from six to 16 weeks of age. The blood pressure-time curve 
      was significantly (P < 0.05) suppressed immediately after administration of 
      DHEAS. There was no difference between the heart rates of control and DHEAS 
      groups. Serum concentrations of corticosterone and dehydrocorticosterone in the 
      DHEAS group were significantly (P < 0.05) lower than those of the control group. 
      The dehydrocorticosterone/corticosterone concentration ratio was, however, 
      significantly (P < 0.05) higher in the DHEAS group, suggesting that treatment 
      with DHEAS enhanced the overall interconversion of corticosterone to 
      dehydrocorticosterone. The activity of 11 beta-HSD in specific organs of the 
      DHEAS group was affected, characteristic changes being increases in the kidney 
      (14-58%), decreases in the liver (11-27%) and no change in the testis. Direct 
      addition of DHEAS to 11 beta-HSD preparations from the kidneys of control SHR had 
      the same effect as that observed in the in-vivo experiments. The fall in serum 
      corticosterone in the DHEAS group is considered to be related, at least partly, 
      to increased activity of kidney 11 beta-HSD. The inverse correlation of kidney 11 
      beta-HSD activity with serum corticosterone and blood pressure (-r = 0.628, P < 
      0.01, and -r = 0.478, P < 0.05, respectively) suggest that DHEAS delayed the 
      development of hypertension in SHR by selective promotion of kidney 11 beta-HSD 
      activity which in turn resulted in lower serum concentrations of corticosterone 
      and its minimal aldosterone-like activity.
FAU - Homma, M
AU  - Homma M
AD  - Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life 
      Science, Japan.
FAU - Onodera, T
AU  - Onodera T
FAU - Hirabatake, M
AU  - Hirabatake M
FAU - Oka, K
AU  - Oka K
FAU - Kanazawa, M
AU  - Kanazawa M
FAU - Miwa, T
AU  - Miwa T
FAU - Hayashi, T
AU  - Hayashi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Glucocorticoids)
RN  - 57B09Q7FJR (Dehydroepiandrosterone Sulfate)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Antihypertensive Agents/*pharmacology
MH  - Blood Pressure/drug effects
MH  - Corticosterone/blood
MH  - Dehydroepiandrosterone Sulfate/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Glucocorticoids/blood
MH  - Heart Rate/drug effects
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Kidney/drug effects/enzymology
MH  - Liver/drug effects/enzymology
MH  - Male
MH  - Rats
MH  - Rats, Inbred SHR
EDAT- 1998/11/20 00:00
MHDA- 1998/11/20 00:01
CRDT- 1998/11/20 00:00
PHST- 1998/11/20 00:00 [pubmed]
PHST- 1998/11/20 00:01 [medline]
PHST- 1998/11/20 00:00 [entrez]
AID - 10.1111/j.2042-7158.1998.tb03325.x [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 1998 Oct;50(10):1139-45. doi: 
      10.1111/j.2042-7158.1998.tb03325.x.