PMID- 12805026
OWN - NLM
STAT- MEDLINE
DCOM- 20031010
LR  - 20220316
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 285
IP  - 4
DP  - 2003 Oct
TI  - Superoxide-NO interaction decreases flow- and agonist-induced dilations of 
      coronary arterioles in Type 2 diabetes mellitus.
PG  - H1404-10
AB  - Type 2 diabetes mellitus (T2-DM) markedly increases the incidence of ischemic 
      heart disease (IHD) and, consequently, mortality. However, the underlying 
      mechanisms leading to IHD in T2-DM are not completely understood. We hypothesized 
      that in T2-DM the regulation of coronary microvascular resistance by local 
      mechanisms is altered. Thus, in coronary arterioles (diameter: approximately 80 
      microm) isolated from male mice with T2-DM (C57BL/KsJ-db/db) and control 
      littermates, responses to changes in intraluminal pressure, flow, and agonists 
      with known mechanisms of action were studied. Increases in pressure (from 20 to 
      120 mmHg) resulted in similar myogenic responses of coronary arterioles of 
      control and db/db mice, whereas dilations in response to cumulative 
      concentrations of ACh and the nitric oxide (NO) donor NONOate were significantly 
      decreased compared with those of control vessels. On the other hand, responses to 
      adenosine were not different between vessels of control and db/db mice. Increases 
      in flow (0-20 microl/min) resulted in dilations of control vessels (maximum: 38 
      +/- 4%) that were inhibited by the NO synthase inhibitor N omega-nitro-L-arginine 
      methyl ester (L-NAME). In contrast, arterioles of db/db mice exhibited greatly 
      reduced dilations to flow (maximum: 4 +/- 6%) that were unaffected by L-NAME. In 
      carotid arteries of db/db mice, superoxide dismutase (SOD)-sensitive, enhanced 
      superoxide production was detected by dihydroethydine staining and lucigenin 
      enhanced chemiluminescence. Correspondingly, intraluminal administration of SOD 
      significantly augmented flow-, ACh-, and NONOate-induced dilations of diabetic 
      arterioles, and then flow- and ACh-induced responses could be inhibited by 
      L-NAME. Collectively, these findings suggest that in T2-DM, due to an enhanced 
      superoxide production, NO mediation of agonist- and flow-induced dilations of 
      coronary arterioles is reduced. This alteration in the regulation of coronary 
      microvascular resistance may contribute to the development of IHD in T2-DM.
FAU - Bagi, Zsolt
AU  - Bagi Z
AD  - Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Koller, Akos
AU  - Koller A
FAU - Kaley, Gabor
AU  - Kaley G
LA  - eng
GR  - HL-46813/HL/NHLBI NIH HHS/United States
GR  - P0-1-HL-43023/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030612
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (Vasodilator Agents)
RN  - 11062-77-4 (Superoxides)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Arterioles/drug effects
MH  - Blood Pressure
MH  - Carotid Arteries/drug effects/enzymology
MH  - Coronary Circulation/*drug effects
MH  - Diabetes Mellitus, Type 2/genetics/*physiopathology
MH  - Drug Interactions
MH  - Male
MH  - Mice
MH  - Nitric Oxide/*pharmacology
MH  - Nitric Oxide Donors/pharmacology
MH  - Stress, Mechanical
MH  - Superoxides/metabolism/*pharmacology
MH  - Vasodilation/*drug effects
MH  - Vasodilator Agents/*pharmacology
EDAT- 2003/06/14 05:00
MHDA- 2003/10/11 05:00
CRDT- 2003/06/14 05:00
PHST- 2003/06/14 05:00 [pubmed]
PHST- 2003/10/11 05:00 [medline]
PHST- 2003/06/14 05:00 [entrez]
AID - 00235.2003 [pii]
AID - 10.1152/ajpheart.00235.2003 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1404-10. doi: 
      10.1152/ajpheart.00235.2003. Epub 2003 Jun 12.