PMID- 15947245
OWN - NLM
STAT- MEDLINE
DCOM- 20051229
LR  - 20131121
IS  - 1524-4636 (Electronic)
IS  - 1079-5642 (Linking)
VI  - 25
IP  - 8
DP  - 2005 Aug
TI  - Type 2 diabetic mice have increased arteriolar tone and blood pressure: enhanced 
      release of COX-2-derived constrictor prostaglandins.
PG  - 1610-6
AB  - OBJECTIVE: Type 2 diabetes mellitus (T2-DM) is frequently associated with 
      vascular dysfunction and elevated blood pressure, yet the underlying mechanisms 
      are not completely understood. We hypothesized that in T2-DM, the regulation of 
      peripheral vascular resistance is altered because of changes in local vasomotor 
      mechanisms. METHODS AND RESULTS: In mice with T2-DM (C57BL/KsJ-(db-)/db-), 
      systolic and mean arterial pressures measured by the tail cuff method were 
      significantly elevated compared with those of control (db+/db-) animals (db/db, 
      146+/-5 and 106+/-2 mm Hg versus control, 133+/-4 and 98+/-4 mm Hg, respectively; 
      P<0.05). Total peripheral resistance, calculated from cardiac output values 
      (measured by echocardiography) and mean arterial pressure were significantly 
      elevated in db/db mice (db/db, 25+/-6 versus control, 15+/-1 mm 
      Hg[middot]mL(-1)[middot]min(-1)). In isolated, pressurized gracilis muscle 
      arterioles (diameter approximately 80 microm) from db/db mice, stepwise increases 
      in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in 
      diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 
      66+/-4% versus control, 79+/-3%). The passive diameters of arterioles (obtained 
      in Ca2+-free solution) and the calculated myogenic index were not significantly 
      different in the 2 groups. The presence of the prostaglandin H2/thromboxane A2 
      receptor antagonist SQ29548 did not affect arteriolar diameters of control mice 
      but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 
      80 mm Hg, 80+/-4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not 
      affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, 
      caused a significant shift in the arteriolar pressure-diameter curve of vessels 
      from db/db mice (at 80 mm Hg, 76+/-3%) but not in those of control mice. Also, in 
      aortas of db/db mice, expression of COX-2 was enhanced compared with controls. 
      CONCLUSIONS: Collectively, these findings suggest that in mice with T2-DM, the 
      basal tone of skeletal muscle arterioles is increased because of an enhanced 
      COX-2-dependent production of constrictor prostaglandins. These alterations in 
      microvascular prostaglandin synthesis may contribute to the increase in 
      peripheral resistance and blood pressure in T2-DM.
FAU - Bagi, Zsolt
AU  - Bagi Z
AD  - Division of Physiology, New York Medical College, Valhalla, NY, USA. 
      bagizs@jaguar.unideb.hu
FAU - Erdei, Nora
AU  - Erdei N
FAU - Toth, Attila
AU  - Toth A
FAU - Li, Wei
AU  - Li W
FAU - Hintze, Thomas H
AU  - Hintze TH
FAU - Koller, Akos
AU  - Koller A
FAU - Kaley, Gabor
AU  - Kaley G
LA  - eng
GR  - HL-43023/HL/NHLBI NIH HHS/United States
GR  - HL-46813/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050609
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Prostaglandins)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Aorta/physiology
MH  - Arachidonic Acid/pharmacology
MH  - Arterioles/physiology
MH  - Blood Pressure/physiology
MH  - Cyclooxygenase 1/metabolism
MH  - Cyclooxygenase 2/*metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism/*physiopathology
MH  - Diabetic Angiopathies/*metabolism/*physiopathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Muscle, Skeletal/blood supply
MH  - Prostaglandins/*metabolism
MH  - Vascular Resistance/physiology
MH  - Vasoconstriction/drug effects/physiology
EDAT- 2005/06/11 09:00
MHDA- 2005/12/31 09:00
CRDT- 2005/06/11 09:00
PHST- 2005/06/11 09:00 [pubmed]
PHST- 2005/12/31 09:00 [medline]
PHST- 2005/06/11 09:00 [entrez]
AID - 01.ATV.0000172688.26838.9f [pii]
AID - 10.1161/01.ATV.0000172688.26838.9f [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1610-6. doi: 
      10.1161/01.ATV.0000172688.26838.9f. Epub 2005 Jun 9.