Hydrogen Peroxide, An Endogenous EDHF, Plays An Important Role In Coronary Autoregulation In Vivo

1
Hydrogen Peroxide, An Endogenous EDHF, Plays An
Important Role In Coronary Autoregulation In Vivo
Toyotaka Yada, Hiroaki Shimokawa, Osamu
Hiramatsu, Tatsuya Kajita, Fumiyuki Shigeto,
Masami Goto, Yasuo Ogasawara,Fumihiko
Kajiya Dept. of Medical Engineering, Kawasaki
Medical School, Kurashiki, JapanDept. of
Cardiovascular Medicine, Kyushu University
Graduate School of Medicine, Fukuoka,
Japan Dept. of Cardiovascular Physiology,
Okayama UniversityGraduate School of Medicine
and Dentistry, Okayama, Japan
(Circulation, T. Yada et al, 2003)
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BackgroundCatalase inhibits EDHF-mediated
Responses to Bradykininin Human Mesenteric
Arteries
Bradykinin 10-7 M
0
0
-10
Relaxation,
Hyperpolarization, ?mV
50

-20
n4

n33
100
-30
6
7
8
9
10
P lt 0.05
BK (- log M)
(T. Matoba and H. Shimokawa et al. Biochem
Biophys. Res. Commun. 2002)
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Coronary Autoregulation
Low Perfusion Pressure
High Perfusion Pressure
mmHg 150
mmHg 150
100
100
50
50
4
AIM
To evaluate the Role of Hydrogen Peroxide as an
Endogenous EDHF and the Possible Interaction
among Nitric Oxide, EDHF and Adenosine in
Coronary Autoregulation of Canine Subepicardial
Microvessels In Vivo.
5
Experimental Setup
Infusion Pump
Blood Flow Velocimeter
Venous Sampling of Coronary Sinus
Windkessel
Arterial Sampling
Roller Pump
CCD Microscope
AoP LVP
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Experimental Protocol
(1) Coronary perfusion pressure was changed in a
stepwise manner from 100 to 70, 50 and 30 mmHg
before and after inhibition of NO synthase
(L-NMMA, 200 µM) or of hydrogen peroxide
(Catalase, 40,000U/kg iv and 240,000U/kg ic) with
L-NMMA. (2) Vasodilator responses of small
arteries (gt100 µm) and arterioles (lt100 µm) were
evaluated by CCD microscope. (3) Coronary venous
samples were drawn, and vascular responses were
evaluated after L-NMMA and Catalase plus
adenosine receptor blockade (8-sulfophenyltheopky
lline, 25 µg/kg ic).
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Vascular Responses to Acetylcholine
Arteriole (lt 100 µm)
Small Artery (gt 100 µm)
30
30
20
20
Change in Diameter
Change in Diameter

10
10


L-NMMA Catalase
0
0
L-NMMA
L-NMMA
L-NMMA Catalase
Control
Control

plt0.05 vs. Control
(Circulation, T. Yada et al, 2003)
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Microvascular Responses during Decreasing
Perfusion Pressure
Perfusion Pressure (mm Hg)
(Circulation, T. Yada et al, 2003)
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Feed-back Arteriolar Responses during Coronary
Autoregulation
Plt0.05 Plt0.01
(Circulation, T. Yada et al, 2003)
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Coronary Venous Adenosine
Compensatory Effect of Adenosine
Arteriolar Responses after Adenosine Receptor
Blockade
Coronary venous adenosine (µM)
Change in Diameter
Perfusion Pressure (mm Hg)
Control diameter (µm)
Plt0.05, Plt0.01 vs. control Plt0.05, Plt0.01
vs. L-NMMA Plt0.01 vs. L-NMMA plus catalase
(Circulation, T. Yada et al, 2003)
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SUMMARY
After NO inhibition, vasodilator responses were
attenuated mainly in small arteries (gt100 µm),
whereas combined infusion of NO inhibition plus
catalase abolished the autoregulatory
vasodilation in both small arteries and
arterioles ( lt100 µm).
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CONCLUSION
Hydrogen peroxide, an endogenous EDHF, plays an
important role of vasodilation in coronary
autoregulation of canine subepicardial
microvessels in vivo.