Diminished arteriolar responses in nitrate tolerance involve ROS and angiotensin II
Departments of 1 Anesthesiology, 2 Medicine, and 3 Biomedical Engineering and 4 Center for Cardiovascular Research, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642 Our purpose was to evaluate hyporesponsivity to nitric oxide (NO)-induced dilation in small arte...
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Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 2002-06, Vol.282 (6), p.H2377-H2385 |
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Zusammenfassung: | Departments of 1 Anesthesiology,
2 Medicine, and 3 Biomedical
Engineering and 4 Center for Cardiovascular
Research, University of Rochester School of Medicine and Dentistry,
Rochester, New York 14642
Our purpose was to evaluate
hyporesponsivity to nitric oxide (NO)-induced dilation in small
arterioles during nitrate tolerance. An Alza osmotic pump was implanted
in the left flank of adult rats ( n = 56) for continuous
administration of nitroglycerin (140 µg/h) or vehicle (propylene
glycol). On postoperative day 3 , arcade (~50-µm
diameter) and terminal (~20 µm) arterioles were observed in the
cremaster preparation with in vivo video microscopy. Local vascular
responses were obtained with micropipette-applied NO donors, with
and without superoxide dismutase (SOD), Mn(III) tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP), or losartan. On day 3 ,
NO-mediated dilation was significantly attenuated in
nitroglycerin-treated rats. Attenuation was greater in the
terminal arterioles compared with the arcades. Control responses were
restored by SOD, MnTBAP, or losartan, suggesting a role for elevated
angiotensin II and reactive oxygen species (ROS) as mediators of the
attenuated NO dilation (nitrate tolerance). Addition of losartan to the
drinking water likewise prevented nitrate tolerance. In summary,
terminal arterioles are affected by nitrates to a greater extent than
the arcade arterioles that feed them, in a process dependent on
angiotensin II and ROS.
microvascular responses; steady vs. pulsatile flow; superoxide |
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ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.00429.2001 |