PMID- 16997891
OWN - NLM
STAT- MEDLINE
DCOM- 20070220
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 292
IP  - 1
DP  - 2007 Jan
TI  - H2O2 increases production of constrictor prostaglandins in smooth muscle leading 
      to enhanced arteriolar tone in Type 2 diabetic mice.
PG  - H649-56
AB  - Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes 
      mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We 
      hypothesized that, in mice with T2-DM, hydrogen peroxide (H(2)O(2)) is involved 
      in the increased synthesis of constrictor prostaglandins, hence enhanced basal 
      tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle 
      arterioles ( approximately 100 microm in diameter) of mice with T2-DM 
      (C57BL/KsJ-db(-)/db(-)) exhibited greater basal tone to increases in intraluminal 
      pressure (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 +/- 
      5%; db/db: 34 +/- 4%, P < 0.05), which was reduced back to control level by 
      catalase (db/db: 24 +/- 4%). Correspondingly, in carotid arteries of db/db mice, 
      the level of dichlorofluorescein-detectable and catalase-sensitive H(2)O(2) was 
      significantly greater. In control arterioles, exogenous H(2)O(2) (0.1-100 
      micromol/l) elicited dilations (maximum, 58 +/- 10%), whereas in arterioles of 
      db/db mice H(2)O(2) caused constrictions (-28 +/- 8%), which were converted to 
      dilations (maximum, 16 +/- 5%) by the thromboxane A(2)/prostaglandin H(2) (TP) 
      receptor antagonist SQ-29548. In addition, arteriolar constrictions in response 
      to the TP receptor agonist U-46619 were not different between the two groups of 
      vessels. Endothelium denudation did not significantly affect basal tone and 
      H(2)O(2)-induced arteriolar responses in either control or db/db mice. Also, in 
      arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was 
      detected in the endothelial layer of vessels. Thus we propose that, in mice with 
      T2-DM, arteriolar production of H(2)O(2) is enhanced, which leads to increased 
      synthesis of the constrictor prostaglandins thromboxane A(2)/prostaglandin H(2) 
      in the smooth muscle cells, which enhance basal arteriolar tone. These 
      alterations may contribute to disturbed regulation of skeletal muscle blood flow 
      in Type 2 diabetes mellitus.
FAU - Erdei, Nora
AU  - Erdei N
AD  - Dept. of Physiology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Bagi, Zsolt
AU  - Bagi Z
FAU - Edes, Istvan
AU  - Edes I
FAU - Kaley, Gabor
AU  - Kaley G
FAU - Koller, Akos
AU  - Koller A
LA  - eng
GR  - HL-46813/HL/NHLBI NIH HHS/United States
GR  - P01-HL-43023/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060922
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Prostaglandins)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Arterioles/drug effects/*physiopathology
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Dose-Response Relationship, Drug
MH  - Hydrogen Peroxide/*administration & dosage
MH  - In Vitro Techniques
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Skeletal/blood supply/drug effects/physiopathology
MH  - Muscle, Smooth, Vascular/drug effects/*physiopathology
MH  - Prostaglandins/*metabolism
MH  - Vasoconstriction/*drug effects
EDAT- 2006/09/26 09:00
MHDA- 2007/02/21 09:00
CRDT- 2006/09/26 09:00
PHST- 2006/09/26 09:00 [pubmed]
PHST- 2007/02/21 09:00 [medline]
PHST- 2006/09/26 09:00 [entrez]
AID - 00596.2006 [pii]
AID - 10.1152/ajpheart.00596.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H649-56. doi: 
      10.1152/ajpheart.00596.2006. Epub 2006 Sep 22.