PMID- 21930604
OWN - NLM
STAT- MEDLINE
DCOM- 20120529
LR  - 20211020
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 589
IP  - Pt 21
DP  - 2011 Nov 1
TI  - Paradoxical effects of streptozotocin-induced diabetes on endothelial dysfunction 
      in stroke-prone spontaneously hypertensive rats.
PG  - 5153-65
LID - 10.1113/jphysiol.2011.213686 [doi]
AB  - Although both diabetes and hypertension are risk factors for cardiovascular 
      disease, the role of hyperglycaemia per se in endothelial dysfunction is 
      controversial. This study was designed to examine whether hyperglycaemia, or 
      streptozotocin-induced diabetes, could aggravate endothelial dysfunction in 
      stroke-prone spontaneously hypertensive rats (SHRSP). Hyperglycaemia was induced 
      by streptozotocin in 2-month-old SHRSP and age-matched normotensive Wistar-Kyoto 
      (WKY) rats. The aorta was isolated 8 weeks after induction of hyperglycaemia to 
      record its function and to examine its morphology with transmission electron 
      microscopy. Endothelial/inducible nitric oxide synthase (eNOS/iNOS) and 
      inducible/constitutive haem oxygenase (HO-1/HO-2) levels were determined with 
      Western blotting. Aortic endothelial function and production of reactive oxygen 
      species and nitric oxide were assayed after incubation in vitro in 
      hyperglycaemic, hyperosmolar solution. Streptozotocin-induced diabetes of 8 weeks 
      duration did not result in endothelial dysfunction in normotensive WKY rats. In 
      contrast, hyperglycaemic WKY rats showed significantly enhanced 
      endothelium-dependent vasodilatation, which was abrogated by simultaneous 
      blocking of NOS and HO. The enhanced vasodilatation was associated with elevation 
      of vascular eNOS and HO-1. Significant endothelial dysfunction and massive 
      macrophage-monocyte infiltration were found in SHRSP aorta (the ratio of the 
      number of macrophages to endothelial cells in the intima, expressed as a 
      percentage, was 20.9 +/- 2.8% in SHRSP versus 1.9 +/- 0.5% in WKY rats, P < 0.01), 
      which was attenuated significantly in hyperglycaemic SHRSP (11.3 +/- 1.6%, P < 0.01 
      versus SHRSP). Acute hyperglycaemia (10 min) aggravated endothelial dysfunction 
      in SHRSP, with a marked increase in intracellular reactive oxygen species and NO 
      production. Sustained in vitro incubation in hyperglycaemic/hyperosmolar 
      conditions (addition of an extra 50 mmol L(-1) of glucose or mannitol to the 
      usual buffer, to produce a final osmolarity of 350 mosmol L(-1)) for 5 h enhanced 
      endothelium-dependent vasodilatation, with elevated vessel NO production and 
      upregulation of eNOS/HO-1 proteins. Sustained hyperglycaemia does not aggravate 
      endothelial dysfunction and macrophage infiltration in SHRSP. 
      Hyperglycaemia/hyperosmolarity-induced upregulation of eNOS and HO-1 may play a 
      role in this paradoxical adaptation of endothelial function.
FAU - Zhong, Mei-Fang
AU  - Zhong MF
AD  - Department of Pharmacology, Ruijin Hospital, Shanghai Jiaotong University School 
      of Medicine, Shanghai, China.
FAU - Shen, Wei-Li
AU  - Shen WL
FAU - Wang, Jian
AU  - Wang J
FAU - Yang, Jie
AU  - Yang J
FAU - Yuan, Wen-Jun
AU  - Yuan WJ
FAU - He, Jin
AU  - He J
FAU - Wu, Ping-Ping
AU  - Wu PP
FAU - Wang, Yuan
AU  - Wang Y
FAU - Zhang, Lan
AU  - Zhang L
FAU - Higashino, Hideaki
AU  - Higashino H
FAU - Chen, Hong
AU  - Chen H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110919
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Vasodilator Agents)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Antihypertensive Agents/pharmacology
MH  - Aorta, Thoracic/metabolism/*physiopathology/ultrastructure
MH  - Diabetes Mellitus, Experimental/metabolism/*physiopathology
MH  - Heme Oxygenase (Decyclizing)/metabolism
MH  - Hyperglycemia/chemically induced/metabolism/*physiopathology
MH  - Hypertension/metabolism/*physiopathology
MH  - In Vitro Techniques
MH  - Macrophages/physiology/ultrastructure
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Nitroprusside/pharmacology
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Rats, Inbred WKY
MH  - Reactive Oxygen Species/metabolism
MH  - Streptozocin
MH  - Tunica Intima/pathology/ultrastructure
MH  - *Vasodilation/drug effects
MH  - Vasodilator Agents/pharmacology
PMC - PMC3225671
EDAT- 2011/09/21 06:00
MHDA- 2012/05/30 06:00
PMCR- 2012/11/01
CRDT- 2011/09/21 06:00
PHST- 2011/09/21 06:00 [entrez]
PHST- 2011/09/21 06:00 [pubmed]
PHST- 2012/05/30 06:00 [medline]
PHST- 2012/11/01 00:00 [pmc-release]
AID - jphysiol.2011.213686 [pii]
AID - 10.1113/jphysiol.2011.213686 [doi]
PST - ppublish
SO  - J Physiol. 2011 Nov 1;589(Pt 21):5153-65. doi: 10.1113/jphysiol.2011.213686. Epub 
      2011 Sep 19.