PMID- 15911738
OWN - NLM
STAT- MEDLINE
DCOM- 20051129
LR  - 20171116
IS  - 1524-4563 (Electronic)
IS  - 0194-911X (Linking)
VI  - 46
IP  - 1
DP  - 2005 Jul
TI  - Chronic tumor necrosis factor-alpha inhibition enhances NO modulation of vascular 
      function in estrogen-deficient rats.
PG  - 76-81
AB  - Tumor necrosis factor-alpha (TNF-alpha) is involved in the pathogenesis of 
      vascular disease. Clinical studies have shown that postmenopausal women have 
      higher serum TNF-alpha levels; however, whether this increase in TNF-alpha is 
      associated with vascular dysfunction is unknown. We investigated whether estrogen 
      deficiency is associated with increased serum TNF-alpha levels and tested the 
      effects of in vivo TNF-alpha inhibition on vascular reactivity. Aged (12 to 15 
      months) Sprague-Dawley rats were ovariectomized and treated with placebo, 
      estrogen, or a TNF-alpha inhibitor (Etanercept; 0.3 mg/kg) for 4 weeks. Serum 
      TNF-alpha was determined by a bioassay, and vascular function was evaluated in 
      the myograph system. Estrogen-deficient animals had higher serum levels of 
      TNF-alpha compared with either estrogen-replaced animals or animals treated with 
      Etanercept. Moreover, in estrogen-deficient rats, TNF-alpha inhibition reduced 
      the constriction of mesenteric arteries to phenylephrine, increased the 
      modulation of this vasoconstriction by the NO synthase inhibitor nitro-l-arginine 
      methyl ester, and decreased the modulation by a superoxide scavenger 
      (Mn(III)tetrakis(4-benzoic acid) porphyrin chloride). Furthermore, 
      endothelium-dependent relaxation was also enhanced by TNF-alpha antagonism. 
      Additionally, vascular expression of endothelial NO synthase was increased in 
      animals treated with Etanercept, whereas the expression of NAD(P)H oxidase 
      gp91phox and p22phox subunits was decreased. These data show that 
      estrogen-deficient female rats have higher bioactive serum TNF-alpha levels 
      compared with estrogen-replaced animals. Moreover, a decrease in serum bioactive 
      TNF-alpha by a soluble TNF-alpha receptor (Etanercept) results in increased 
      modulation of vascular function by NO. These observations suggest that TNF-alpha 
      could be a mediator of vascular dysfunction associated with estrogen deficiency.
FAU - Arenas, Ivan A
AU  - Arenas IA
AD  - Perinatal Research Center, Department of Obstetrics and Gynecology, University of 
      Alberta, Edmonton, Alberta, T6G 2S2, Canada.
FAU - Armstrong, Stephen J
AU  - Armstrong SJ
FAU - Xu, Yi
AU  - Xu Y
FAU - Davidge, Sandra T
AU  - Davidge ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050523
PL  - United States
TA  - Hypertension
JT  - Hypertension (Dallas, Tex. : 1979)
JID - 7906255
RN  - 0 (Estrogens)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - OP401G7OJC (Etanercept)
SB  - IM
CIN - Hypertension. 2005 Jul;46(1):21-2. PMID: 15911737
MH  - Animals
MH  - Estrogens/*deficiency/pharmacology
MH  - Etanercept
MH  - Female
MH  - Immunoglobulin G/*pharmacology
MH  - Mesenteric Arteries/enzymology
MH  - NADPH Oxidases/metabolism
MH  - Nitric Oxide/*metabolism
MH  - Ovariectomy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors/metabolism
MH  - Vasomotor System/*physiopathology
EDAT- 2005/05/25 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/05/25 09:00
PHST- 2005/05/25 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/05/25 09:00 [entrez]
AID - 01.HYP.0000168925.98963.ef [pii]
AID - 10.1161/01.HYP.0000168925.98963.ef [doi]
PST - ppublish
SO  - Hypertension. 2005 Jul;46(1):76-81. doi: 10.1161/01.HYP.0000168925.98963.ef. Epub 
      2005 May 23.