PMID- 10801763
OWN - NLM
STAT- MEDLINE
DCOM- 20000530
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 101
IP  - 18
DP  - 2000 May 9
TI  - Investigation into the sources of superoxide in human blood vessels: angiotensin 
      II increases superoxide production in human internal mammary arteries.
PG  - 2206-12
AB  - BACKGROUND: Increased vascular superoxide anion (.O(2)(-)) production contributes 
      to endothelial dysfunction and hypertension in animal models of cardiovascular 
      disease. Observations in experimental animals suggest that angiotensin II (Ang 
      II) increases.O(2)(-) production by activation of vascular NAD(P)H oxidase. We 
      studied the sources of.O(2)(-) production in human blood vessels and investigated 
      whether, and by what mechanism, Ang II might alter vascular.O(2)(-) production. 
      METHODS AND RESULTS: Internal mammary arteries (IMAs) and saphenous veins (SVs) 
      were collected at the time of cardiac surgery. Vessels were incubated in Krebs 
      buffer at 37 degrees C.O(2)(-) was measured by lucigenin chemiluminescence. 
      Basal. O(2)(-) concentrations were greater in IMAs than SVs. Inhibitors of 
      NAD(P)H oxidase (10 micromol/L to 200 micromol/L diphenyleneiodonium) and 
      xanthine oxidase (1 mmol/L allopurinol) caused reductions in.O(2)(-) 
      concentrations in both IMAs and SVs. Western blotting of superoxide dismutase 
      proteins demonstrated similar expression in IMAs and SVs. Vessels were also 
      incubated in the presence or absence of Ang II (1 pmol/L to 1 micromol/L). Ang II 
      increased.O(2)(-) production in IMAs at 4 hours of incubation (control, 978+/-117 
      pmol. min(-1). mg(-1); 1 micromol/L of Ang II, 1690+/-213 pmol. min(-1). mg(-1); 
      n=27, P=0.0001, 95% CI 336, 925) but not in SVs. This effect was completely 
      inhibited by coincubation of IMAs with DPI (100 micromol/L), a nonspecific Ang II 
      antagonist ([sar(1), thre(8)]-Ang II, 1 micromol/L) and a specific Ang II type 1 
      (AT(1)) receptor antagonist (losartan, 1 micromol/L). Conclusions-. O(2)(-) 
      production is greater in human IMAs than in SVs. NAD(P)H oxidase and xanthine 
      oxidase are sources of.O(2)(-) production in these vessels. The vasoactive 
      peptide Ang II increases.O(2)(-) production in human arteries by an AT(1) 
      receptor-dependent mechanism.
FAU - Berry, C
AU  - Berry C
AD  - Department of Medicine and Therapeutics, University of Glasgow, Glasgow, UK. 
      colin.berry@clinmed.gla.ac.uk
FAU - Hamilton, C A
AU  - Hamilton CA
FAU - Brosnan, M J
AU  - Brosnan MJ
FAU - Magill, F G
AU  - Magill FG
FAU - Berg, G A
AU  - Berg GA
FAU - McMurray, J J
AU  - McMurray JJ
FAU - Dominiczak, A F
AU  - Dominiczak AF
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Vasoconstrictor Agents)
RN  - 11062-77-4 (Superoxides)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Aged
MH  - Angiotensin II/metabolism/*pharmacology
MH  - Coronary Disease/*blood/physiopathology
MH  - Female
MH  - Humans
MH  - Male
MH  - Mammary Arteries/*metabolism/physiopathology
MH  - Middle Aged
MH  - Saphenous Vein/metabolism
MH  - Superoxides/*blood
MH  - Vasoconstrictor Agents/metabolism/*pharmacology
EDAT- 2000/05/10 00:00
MHDA- 2000/06/03 00:00
CRDT- 2000/05/10 00:00
PHST- 2000/05/10 00:00 [pubmed]
PHST- 2000/06/03 00:00 [medline]
PHST- 2000/05/10 00:00 [entrez]
AID - 10.1161/01.cir.101.18.2206 [doi]
PST - ppublish
SO  - Circulation. 2000 May 9;101(18):2206-12. doi: 10.1161/01.cir.101.18.2206.