PMID- 11856543
OWN - NLM
STAT- MEDLINE
DCOM- 20020607
LR  - 20190822
IS  - 0039-128X (Print)
IS  - 0039-128X (Linking)
VI  - 67
IP  - 3-4
DP  - 2002 Mar
TI  - 11 beta-Hydroxysteroid dehydrogenase antisense affects vascular contractile 
      response and glucocorticoid metabolism.
PG  - 195-201
AB  - Glucocorticoids (GC's) are metabolized in vascular tissue by two isoforms of 11 
      beta-hydroxysteroid dehydrogenase (11 beta-HSD). 11 beta-HSD2 is unidirectional 
      and metabolizes GC's to their respective inactive 11-dehydro derivatives. 11 
      beta-HSD1 is bi-directional, also possessing reductase activity and thus the 
      ability to regenerate active GC from the 11-dehydro derivatives. In vascular 
      tissue, GC's amplify the pressor responses to catecholamines and angiotensin II 
      and may down-regulate certain depressor systems such as nitric oxide and 
      prostaglandins. We hypothesize that both 11 beta-HSD2 and 11 beta-HSD1 regulate 
      GC levels in vascular tissue and are part of additional mechanisms that control 
      vascular tone. We examined the effects of specific antisense oligomers to 11 
      beta-HSD2 and 11 beta-HSD1 on GC metabolism and contractile response to 
      phenylephrine (PE) in rat aortic rings. In aortic rings incubated (24 h) with 
      corticosterone (B) (10 nmol/l) and 11 beta-HSD2 antisense (3 micromol/l), the 
      contractile response to graded concentrations of PE (PE: 10 nmol/l - 1 
      micromol/l) were significantly (P < 0.05) increased compared to rings incubated 
      with B and 11 beta-HSD2 nonsense. 11 beta-HSD1 antisense oligomers also enhanced 
      the ability of B to amplify the contractile response to PE. In addition, 11 
      beta-HSD2 and 11 beta-HSD1 antisense also decreased the metabolism of B to 
      11-dehydro-B. 11-Dehydro-B (100 nmol/l) also amplified the contractile response 
      to PE in aortic rings (P < 0.01), most likely due to the generation of active 
      corticosterone by 11 beta-HSD1-reductase; this effect was significantly 
      attenuated by 11 beta-HSD1 antisense. 11 beta-HSD1 antisense also caused a marked 
      decrease in the metabolism of 11-dehydro-B back to B by 11 beta-HSD1-reductase. 
      These findings underscore the importance of 11 beta-HSD2 and 11 beta-HSD1 in 
      regulating local concentrations of GC's in vascular tissue. They also indicate 
      that decreased 11 beta-HSD2 activity may be a possible mechanism in hypertension 
      and that 11 beta-HSD1-reductase may be a possible target for anti-hypertensive 
      therapy.
FAU - Souness, Graham W
AU  - Souness GW
AD  - The Miriam Hospital, Providence, RI, USA.
FAU - Brem, Andrew S
AU  - Brem AS
FAU - Morris, David J
AU  - Morris DJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Steroids
JT  - Steroids
JID - 0404536
RN  - 0 (Glucocorticoids)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 10028-17-8 (Tritium)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 2)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - FO4V44A3G3 (11-dehydrocorticosterone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 2
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Animals
MH  - Aorta, Thoracic
MH  - Corticosterone/*analogs & derivatives/metabolism
MH  - Endothelium, Vascular/physiology
MH  - Glucocorticoids/*metabolism
MH  - Hydroxysteroid Dehydrogenases/*genetics/metabolism
MH  - Male
MH  - Muscle Contraction/*drug effects
MH  - Muscle, Smooth, Vascular/*physiology
MH  - Oligonucleotides, Antisense/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Tritium
EDAT- 2002/02/22 10:00
MHDA- 2002/06/12 10:01
CRDT- 2002/02/22 10:00
PHST- 2002/02/22 10:00 [pubmed]
PHST- 2002/06/12 10:01 [medline]
PHST- 2002/02/22 10:00 [entrez]
AID - S0039128X01001489 [pii]
AID - 10.1016/s0039-128x(01)00148-9 [doi]
PST - ppublish
SO  - Steroids. 2002 Mar;67(3-4):195-201. doi: 10.1016/s0039-128x(01)00148-9.