PMID- 8969942
OWN - NLM
STAT- MEDLINE
DCOM- 19970313
LR  - 20191024
IS  - 0743-5800 (Print)
IS  - 0743-5800 (Linking)
VI  - 22
IP  - 4
DP  - 1996 Nov
TI  - Endogenous 11 beta-hydroxysteroid dehydrogenase inhibitors and their role in 
      glucocorticoid Na+ retention and hypertension.
PG  - 793-801
AB  - 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) metabolizes active 
      glucocorticoids to their inactive 11-dehydro products and protects renal 
      mineralocorticoid receptors from the high circulating levels of endogenous 
      glucocorticoids. 11 beta-HSD has been suggested to be important not only in the 
      control of renal sodium retention but also blood pressure. We had previously 
      shown that 11 alpha- and 11 beta-hydroxyprogesterone (11 alpha- and 11 beta-OHP) 
      were (I) potent inhibitors of 11 beta-HSD (Isoforms 1 and 2) activity in vitro, 
      (ii) able to confer mineralocorticoid (MC) activity upon corticosterone (B) in 
      vivo and (iii) hypertensinogenic when chronically infused into Sprague-Dawley 
      (SD) rats. In addition we also showed that 3 alpha,5B-tetrahydroprogesterone (3 
      alpha,5B-THP) and chenodeoxycholic acid (CDCA) were potent inhibitors of 11 
      beta-HSD1 activity but not 11 beta-HSD2 activity, however, these substances were 
      still able to confer MC activity upon B in the adrenalectomized rat. To assess 
      the possible blood pressure modulating effects of 3 alpha,5B-THP and CDCA we have 
      now infused these substances into intact SD rats continuously for 14 days. Both 3 
      alpha,5B-THP and CDCA caused a significant elevation in blood pressure within 
      seven days, an effect that persisted throughout the 14-day infusion. These 
      results show that both 3 alpha,5B-THP and CDCA are hypertensinogenic in the rat 
      and that the inhibition of either 11 beta-HSD2 or 11 beta-HSD1 activity by 
      endogenous progesterone metabolites and CDCA may be involved in the pathology of 
      hypertension.
FAU - Morris, D J
AU  - Morris DJ
AD  - Department of Pathology and Laboratory Medicine, Miriam Hospital, Lifespan and 
      Brown University School of Medicine, Providence, RI 02906, USA.
FAU - Souness, G W
AU  - Souness GW
LA  - eng
GR  - DK21404/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Endocr Res
JT  - Endocrine research
JID - 8408548
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glucocorticoids)
RN  - 0 (Isoenzymes)
RN  - 0GEI24LG0J (Chenodeoxycholic Acid)
RN  - 9NEZ333N27 (Sodium)
RN  - BXO86P3XXW (Pregnanolone)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Chenodeoxycholic Acid/pharmacology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Glucocorticoids/*metabolism
MH  - Hydroxysteroid Dehydrogenases/*antagonists & inhibitors
MH  - Hypertension/*etiology
MH  - Isoenzymes/antagonists & inhibitors
MH  - Kinetics
MH  - Male
MH  - Pregnanolone/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sodium/*metabolism
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1080/07435809609043778 [doi]
PST - ppublish
SO  - Endocr Res. 1996 Nov;22(4):793-801. doi: 10.1080/07435809609043778.